Apoptosis
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"One of the mechanisms by which CELL DEATH occurs (compare with NECROSIS and AUTOPHAGOCYTOSIS). Apoptosis is the mechanism responsible for the physiological deletion of cells and appears to be intrinsically programmed. It is characterized by distinctive morphologic changes in the nucleus and cytoplasm, chromatin cleavage at regularly spaced sites, and the endonucleolytic cleavage of genomic DNA; ( DNA FRAGMENTATION); at internucleosomal sites. This mode of cell death serves as a balance to mitosis in regulating the size of animal tissues and in mediating pathologic processes associated with tumor growth." (Source: MeSH)

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Latest Research Publications

This list of publications is regularly updated (Source: PubMed).

Haghighitalab A, Matin MM, Bahrami AR, et al.
In vitro investigation of anticancer, cell-cycle-inhibitory, and apoptosis-inducing effects of diversin, a natural prenylated coumarin, on bladder carcinoma cells.
Z Naturforsch C. 2014 Mar-Apr; 69(3-4):99-109 [PubMed] Related Publications
Chemotherapy is one of the main strategies for reducing the rate of cancer progression or, in some cases, curing the tumour. Since a great number of chemotherapeutic agents are cytotoxic compounds, i. e. similarly affect normal and neoplastic cells, application of antitumour drugs is preferred in cancer management and therapy. In this study, the cytotoxicity of diversin was evaluated in 5637 cells, a transitional cell carcinoma (TCC) subline (bladder carcinoma), and normal human fibroblast cells using the 3-(4,5-dimethyl-2-thiazolyl)-2,5-diphenyl-2H-tetrazolium bromide (MTT) assay. Chromatin condensation and DNA damage induced by diversin were also determined by means of 4',6-diamidino-2-phenylindole (DAPI) staining and the comet assay, respectively. In addition, the mechanism of action of diversin was studied in more detail by the caspase 3 colourimetric assay and flow cytometry-based cell-cycle analyses (PI staining). Our results revealed that diversin has considerable cytotoxic effects in 5637 cells, but not on HFF3 (human foreskin fibroblast) and HDF1 (human dermal fibroblast) cells. Further studies showed that diversin exerts its cytotoxicity via induction of chromatin condensation, DNA damage, and activation of caspase 3 in 5637 cells. In addition, flow cytometric analyses revealed that 5637 cells are mostly arrested at the G2 phase of the cell cycle in the presence of diversin.

Related: Bladder Cancer Bladder Cancer - Molecular Biology


Ye L, Yao XD, Wan FN, et al.
MS4A8B promotes cell proliferation in prostate cancer.
Prostate. 2014; 74(9):911-22 [PubMed] Related Publications
BACKGROUND: Prostate cancer cells must maintain or achieve the further ability of proliferation during the progression. The molecular mechanisms, however, remain poorly understood. We identified a novel oncogene, termed membrane-spanning 4-domains, subfamily A, member 8B (MS4A8B), over-expressed in prostate cancer.
METHODS: We firstly detected MS4A8B mRNA in 13 types of paired human normal and cancer tissues by real-time polymerase chain reaction (RT-PCR). In 140 clinically localized prostate cancer samples from radical prostatectomy, immunohistochemical staining was performed to study MS4A8B and PCNA protein level as an index of proliferative activity, TUNEL staining as an index of apoptosis. As MS4A8B RNAi and cDNA transfection technologies were used, the effect of MS4A8B on cellular vitality was determined in vitro and in vivo.
RESULTS: MS4A8B mRNA was over-expressed specifically in prostate cancer. Positive ratios of MS4A8B protein expression were 1.94%, 5.92%, and 62.8% in benign, HPIN and prostate cancer, respectively. Moreover, MS4A8B was positively associated with Gleason score, the proliferation index. In vitro, MS4A8B knockdown resulted in G1 -S cell cycle arrest and descended vitality, MS4A8B over-expression with accelerated S phase entry, elevated vitality in prostate cancer cells. Moreover, it was also found that expression of MS4A8B led to changes of Cyclin D1 , Cyclin E1 and PCNA. LNCaP cells transfected with sh-MS4A8B lentivirus particles grew more slowly when subcutaneously injected into the flanks of nude mice.
CONCLUSIONS: We conclude that the expression of MS4A8B expression promotes cell proliferation and plays an important role in carcinogenesis and progression of prostate cancer.

Related: Prostate Cancer KLK3


Kwon HY, Kim KS, An HK, et al.
Triptolide induces apoptosis through extrinsic and intrinsic pathways in human osteosarcoma U2OS cells.
Indian J Biochem Biophys. 2013; 50(6):485-91 [PubMed] Related Publications
Triptolide, a diterpene derived from Tripterygium wilfordii Hook f., a Chinese medicinal herb, has been reported to inhibit cell proliferation and induce apoptosis in various human cancer cells, but its anticancer effects on human osteosarcoma cells have not yet been elucidated. In this study, we investigated whether triptolide induces apoptosis in human osteosarcoma cells and the underlying molecular mechanisms. We firstly demonstrated that triptolide inhibited cell growth and induced apoptosis in U2OS cells. Western blot analysis showed that the levels of procaspase-8, -9, Bcl-2, Bid and mitochondrial cytochrome c were downregulated in triptolide-treated U2OS cells, whereas the levels of Fas, FasL, Bax, cytosolic cytochrome c, cleaved caspase-3 and cleaved PARP were upregulated. These results suggest that triptolide induces apoptosis in U2OS cells by activating both death receptor and mitochondrial apoptotic pathways.

Related: Mitochondrial Mutations in Cancer Osteosarcoma


Shen P, Sun J, Xu G, et al.
KLF9, a transcription factor induced in flutamide-caused cell apoptosis, inhibits AKT activation and suppresses tumor growth of prostate cancer cells.
Prostate. 2014; 74(9):946-58 [PubMed] Related Publications
BACKGROUND: Kruppel-like factors (KLFs) are involved in various biological processes; emerging studies have indicated that KLF9 plays a critical role in regulating tumorigenesis. The role of KLF9 in prostate cancer (PCa), however, has not yet been investigated.
METHODS: The expression of KLF members, AKT- and apoptosis-related proteins were analyzed by Western blot or qRT-PCR. Tet-On inducible KLF9 expression was established for the evaluation of the effects of KLF9 on cell proliferation, apoptosis, and xenograft tumor growth in nude mice. Cell cycle and apoptosis were determined by flow cytometry.
RESULTS: KLF9 was induced in a time-dependent manner in flutamide-caused apoptosis, and knockdown of KLF9 significantly decreased flutamide-induced growth inhibition and apoptosis in LNCaP cells. The levels of KLF9 were relatively lower in PCa cell lines, particularly in androgen-independent cell lines compared with those in nontumorous prostate epithelial cell lines. Overexpression of KLF9 dramatically suppressed cell proliferation and caused cell cycle arrest in the G2/M phase and cell apoptosis in the androgen-independent cell lines, PC3 and DU145. Intriguingly, KLF9 expression severely suppressed the activation of AKT and its downstream targets. AKT reactivation partially rescued the KLF9-mediated inhibitory effects on the proliferation of PCa cells. More importantly, we found that KLF9 overexpression efficiently inhibited the xenograft tumor growth of PCa cells.
CONCLUSIONS: These data collectively showing that KLF9 substantially inhibits AKT activation and abrogates tumor growth of PCa cells, suggest the potential of either genetic or pharmacological activation of KLF9 in the therapeutic treatment of castration-resistant PCa.

Related: AKT1


Sun C, Xu S, Guo J, et al.
The inhibitory and apoptotic effects of docetaxel-loaded mesoporous magnetic colloidal nanocrystal clusters on bladder cancer T24 cells in vitro.
J Biomed Nanotechnol. 2014; 10(3):455-62 [PubMed] Related Publications
Mesoporous magnetic colloidal nanocrystal clusters (MCNCs) are featured with high magnetization, adequate surface area, excellent colloidal stability, good biocompatibility, and acid degradability. It is thus highly anticipated that MCNCs can serve as vehicles for target drug delivery. Herein, the mesoporous MCNCs stabilized by poly(gamma-glutamic acid) (PGA) were fabricated by the modified solvothermal route, showing a high specific surface area (126.4 m2/g), strong magnetic response (63 emu/g) and appropriate mesoporosity including a large pore volume (0.27 cm3/g) and accessible pore size (8.1 nm). Docetaxel (DOC) was then loaded in the resultant MCNCs using the nanoprecipitation method, and a high drug loading capacity was achieved up to 24 wt%. The chemotherapeutic effect and mechanism of DOC-MCNC conjugates in bladder cancer was evaluated in vitro. A series of analyses for cell uptake, cell viability, cell cycle, cell apoptosis and some cell proteins were performed by transmission electron microscopy, MTT assay, flow cytometry, cell nuclei staining, Annexin V staining assay, western blot assay and caspase-3 activity assay, respectively. The results demonstrated that DOC-MCNC conjugates enhanced the inhibitory effect by hampering mitoschisis and increased the apoptotic effect by changing the expression of apoptosis-related proteins in T24 cells, substantially proving their remarkable efficiency in treatment of bladder cancer.

Related: Bladder Cancer Bladder Cancer - Molecular Biology Docetaxel


Guo Y, Shan Q, Gong Y, et al.
Curcumin induces apoptosis via simultaneously targeting AKT/mTOR and RAF/MEK/ERK survival signaling pathways in human leukemia THP-1 cells.
Pharmazie. 2014; 69(3):229-33 [PubMed] Related Publications
BACKGROUND: Curcumin is a multi-targeted anti-cancer agent. However, there are few studies on its anti-leukemia activity in human acute monocytic leukemia. Here, we study the effect and mechanisms of curcumin on acute monocytic leukemia.
METHODS: The acute monocytic leukemia cell line THP-1 was used as in vitro cell model to explore the anti-leukemia effects and mechanisms of curcumin. Cell proliferation was measured by MTT assay, cell apoptosis bodies were observed using a light microscope, cell apoptosis rate was evaluated by flow cytometry, and the expression alterations of growth-sinaling proteins were detected by Western blotting.
RESULTS: Curcumin inhibited cell proliferation and induced cell apoptosis in time- and dose- dependent manner in THP-1 cells. Curcumin significantly inhibited the activations of AKT/mTOR and RAF/MEK/ERK signaling pathways simultaneously.
CONCLUSION: This study demonstrates that curcumin inhibits proliferation and induces apoptosis in THP-1 cells via inhibiting the activations of AKT/mTOR and RAF/MEK/ERK signaling pathways simultaneously. Our data suggest that curcumin is a promising anti-tumor agent in acute monocytic leukemia.

Related: Acute Myeloid Leukemia (AML)


Amato KR, Wang S, Hastings AK, et al.
Genetic and pharmacologic inhibition of EPHA2 promotes apoptosis in NSCLC.
J Clin Invest. 2014; 124(5):2037-49 [PubMed] Free Access to Full Article Related Publications
Genome-wide analyses determined previously that the receptor tyrosine kinase (RTK) EPHA2 is commonly overexpressed in non-small cell lung cancers (NSCLCs). EPHA2 overexpression is associated with poor clinical outcomes; therefore, EPHA2 may represent a promising therapeutic target for patients with NSCLC. In support of this hypothesis, here we have shown that targeted disruption of EphA2 in a murine model of aggressive Kras-mutant NSCLC impairs tumor growth. Knockdown of EPHA2 in human NSCLC cell lines reduced cell growth and viability, confirming the epithelial cell autonomous requirements for EPHA2 in NSCLCs. Targeting EPHA2 in NSCLCs decreased S6K1-mediated phosphorylation of cell death agonist BAD and induced apoptosis. Induction of EPHA2 knockdown within established NSCLC tumors in a subcutaneous murine model reduced tumor volume and induced tumor cell death. Furthermore, an ATP-competitive EPHA2 RTK inhibitor, ALW-II-41-27, reduced the number of viable NSCLC cells in a time-dependent and dose-dependent manner in vitro and induced tumor regression in human NSCLC xenografts in vivo. Collectively, these data demonstrate a role for EPHA2 in the maintenance and progression of NSCLCs and provide evidence that ALW-II-41-27 effectively inhibits EPHA2-mediated tumor growth in preclinical models of NSCLC.

Related: Non-Small Cell Lung Cancer Lung Cancer


Chaotham C, Pongrakhananon V, Sritularak B, Chanvorachote P
A Bibenzyl from Dendrobium ellipsophyllum inhibits epithelial-to-mesenchymal transition and sensitizes lung cancer cells to anoikis.
Anticancer Res. 2014; 34(4):1931-8 [PubMed] Related Publications
BACKGROUND: Anti-metastasis therapy may become the potential means of improving survival of cancer patients. As the ability of cancer cells to change phenotype from epithelial to mesenchymal has been recognized as an important hallmark of cancer metastasis, this study provides information regarding the effect of a bibenzyl, namely 4,5,4'-trihydroxy-3,3'-dimethoxybibenzyl (TDB), isolated from Dendrobium ellipsophyllum, in inhibiting epithelial-to-mesenchymal transition (EMT) and sensitization of lung cancer cells to anoikis.
MATERIALS AND METHODS: Human lung cancer H292 cells were treated with non-cytotoxic doses of TDB for 24 h prior to evaluation of anoikis and anchorage-independent growth. The proteins relevant to EMT and anoikis resistance were examined in TDB-treated H292 cells via western blot analysis.
RESULTS: A significant increase in apoptosis induced by cell detachment was found in TDB-treated H292 cells. The formation of tumor in anchorage-independent growth assay was found to be dramatically reduced in response to the compound. Furthermore, western blot analysis of proteins involved in EMT revealed that treatment with TDB resulted in the increase of E-cadherin and the decrease of vimentin and transcription factor SNAIL, indicating EMT suppression. Concomitantly with EMT inhibition, the activity of pro-survival pathways, including activated protein kinase B (pAKT) and activated extracellular signal-regulated kinase (pERK), were found to be significantly reduced.
CONCLUSION: Because EMT, anoikis resistance and anchorage-independent growth are among important factors facilitating cancer metastasis, TDB shows potential to be developed as an anti-metastasis agent.

Related: Lung Cancer Signal Transduction


Vaeteewoottacharn K, Mitchai M, Srikoon P, et al.
Potent reactive oxygen species-JNK-p38 activation by sodium salicylate potentiates death of primary effusion lymphoma cells.
Anticancer Res. 2014; 34(4):1865-71 [PubMed] Related Publications
BACKGROUND: Primary effusion lymphoma (PEL) is a rare but aggressive form of non-Hodgkin's B-cell lymphoma in immunodeficient patients. Resistance to conventional chemotherapeutic regimens is common in PEL and contributes to a very poor prognosis; hence, novel potent anti-PEL agents are required. Anticancer effects of non-steroidal anti-inflammatory drugs (NSAIDs) are well-established in epithelial cancer but are unclear in hematological malignancies. Therefore, the anticancer activities of selected NSAIDs, sodium salicylate (NaS), on PEL cell lines are of interest.
MATERIALS AND METHODS: Anti-proliferation of NaS on PEL cell lines was shown by MTT. Apoptosis induction and caspase activations were determined by flow cytometry analysis. ROS production was accessed by DCFH-DA. Western blot was performed to determine molecular mechanisms.
RESULTS: NaS effectively inhibited cell proliferation of all PEL cell lines. Caspase-dependent apoptosis was demonstrated and simultaneous induction of reactive oxygen species production and c-Jun N-terminal kinases (JNK)-p38 activation was observed prior to apoptosis induction, and these might be responsible for NaS-induced apoptosis.
CONCLUSION: Significant anticancer effects of NaS on PEL cell lines were found. A novel role of NaS for PEL treatment is suggested.


Figueiró F, Mendes FB, Corbelini PF, et al.
A monastrol-derived compound, LaSOM 63, inhibits ecto-5'nucleotidase/CD73 activity and induces apoptotic cell death of glioma cell lines.
Anticancer Res. 2014; 34(4):1837-42 [PubMed] Related Publications
BACKGROUND/AIM: Glioblastoma multiforme is the most malignant type of glioma. Ecto-5'-nucleotidase (ecto-5'NT), a glioma-overexpressed enzyme can induce a protective effect on tumor cells. Monastrol, a kinesin spindle protein-specific inhibitor, is reported to be an interesting prototype for cancer therapy. We describe the effect of LaSOM 63, a monastrol derivative, on ecto-5'NT activity and on glioma cell survival.
MATERIALS AND METHODS: Glioma cells were treated with LaSOM 63 and 3-(4,5-dimethylthiazol-2-yl)-2,5-diphenyltetrazolium bromide (MTT), trypan blue assay (viability), flow cytometry (cell cycle/cell death) and malachite green method for ecto-5'NT activity were carried out. Results and Discussion: Treatment with LaSOM 63 reduces glioma cell viability and cell growth. In contrast to monastrol, LaSOM 63 did not cause glioma cell-cycle arrest, but inhibited ecto-5'NT enzyme activity. Furthermore, this compound induces apoptotic death of C6 and U138 glioma cells.
CONCLUSION: LaSOM 63 may be useful for in vivo experiments on the treatment of GBM.


Lai CK, Rao YK, Chang KR, et al.
3,3',4', 5'-Tetramethoxychalcone inhibits human oral cancer cell proliferation and migration via p53-mediated mitochondrial-dependent apoptosis.
Anticancer Res. 2014; 34(4):1811-9 [PubMed] Related Publications
BACKGROUND/AIM: The current study aimed to identify an attractive target against human oral squamous cell carcinoma (OSCC).
MATERIALS AND METHODS: The effect of 3,3',4',5'-tetramethoxychalcone (TMC) on OSCC cell proliferation, cell-cycle phase distribution, expression of markers of cell apoptosis, and cell migration were analyzed by 3-(4,5-dimethylthiazol-2-yl)-2,5-diphenyltetrazolium bromide assay, flow cytometry, western blot, and transwell migration assay, respectively.
RESULTS: Experimental results revealed that TMC inhibited the OSCC cell proliferation (fifty percent inhibitory concentrations range=1.0-4.5 μM) by inducing G2/M phase arrest of the cell cycle. TMC caused DNA double-strand breaks, and enhanced expression of caspase-3 and -9, poly (ADP-ribose) polymerase, cytochrome c, calpain-1 and -2, phosphorylation of histone H2AX, phosphorylation of checkpoint kinases 2, p53, BCL2-antagonist/killer and BCL2-associated × protein, while reducing the mitochondrial membrane potential, and expression of B-cell lymphoma-2. In addition, TMC reduced the migration potential of OSCC cells by attenuating the C-C chemokine ligand 5/C-C chemokine receptor type 5 axis.
CONCLUSION: These data indicate that TMC may be considered an interesting target for further development of chemotherapeutic agents against oral cancer.

Related: Mitochondrial Mutations in Cancer Oral Cancer TP53


Lee KH, Ho WY, Wu SJ, et al.
Behavior-selective apoptotic capacity of 4-(3,4,5-Trimethoxyphenoxy) benzoic acid and its methyl derivatives on two breast cancer cell lines.
Anticancer Res. 2014; 34(4):1801-9 [PubMed] Related Publications
Breast cancer is one of the most common tumors in females. The therapeutic resistance of breast cancer has motivated the development of new agents for prevention and treatment. For the present study, several compounds were designed and analyzed for their antitumor activity in many cancer cell lines. 4-(3,4,5-Trimethoxyphenoxy) benzoic acid (compound 1) and its derivatives were selected for studying the anti-proliferative and cytotoxic effects on five human cancer cell lines. Results indicated that compounds 1 and 2 significantly suppressed the cell viability of MCF-7 and MDA-MB-468 cancer cells. However, compounds 1 and 2 had only minor effects on HepG2, Huh-7, and Hela cells. Moreover, compounds 1 and 2 exhibited a novel anti-tumor activity through the induction of cell-cycle arrest at G2/M and apoptosis in MCF-7 and MDA-MB-486 breast cancer cells. Both compounds reduced colony-forming ability in MCF-7 cells. Flow cytometric analysis indicated that caspase-3 activity was increased in response to treatment with compounds 1 and 2. Taken together, these findings suggest that the novel compounds 1 and 2 are potential anticancer agents with clinical promise for breast cancer therapy.

Related: Breast Cancer


Chen C, Ono M, Takeshima M, Nakano S
Antiproliferative and apoptosis-inducing activity of nobiletin against three subtypes of human breast cancer cell lines.
Anticancer Res. 2014; 34(4):1785-92 [PubMed] Related Publications
UNLABELLED: Although nobiletin has a potent antitumor activity against several types of human cancers, its inhibitory effects and possible mechanisms of action on breast cancer cells with different hormone receptor and HER2 status remains unknown.
MATERIALS AND METHODS: Using hormone receptor-positive MCF-7, HER2-positive SK-BR-3, and triple-negative MDA-MB-468 cell lines, we investigated the antitumor mechanisms of nobiletin.
RESULTS: Nobiletin exhibited dose- and time-dependent antitumor activity against these different subtypes of cell lines, with the greatest inhibition observed against the MDA-MB-468 cell line. Nobiletin induced cell-cycle arrest at the G0/G1 phase by suppressing ERK1/2 activity, with concomitant cyclin-D1 suppression and p21 up-regulation. Nobiletin induced apoptotic cell death by reducing Bcl-xL expression, without affecting Bax levels, and inhibited the activity of AKT and downstream mTOR in MDA-MB-468 cells, but not in other cell lines.
CONCLUSION: The predominant anticancer activity of nobiletin in MDA-MB-468 cells suggests a potential role of nobiletin for the prevention of triple-negative breast cancer.

Related: Breast Cancer


Kaku Y, Tsuchiya A, Kanno T, et al.
Dipalmitoleoyl-phosphatidylethanolamine induces apoptosis of NCI-H28 malignant mesothelioma cells.
Anticancer Res. 2014; 34(4):1759-64 [PubMed] Related Publications
BACKGROUND/AIM: The phospholipid phosphatidylethanolamine regulates a wide range of cellular processes. The present study investigated the antitumor effect of 1,2-dipalmitoleoyl-sn-glycero-3-phosphoethanolamine (DPPE) on malignant pleural mesothelioma cells.
MATERIALS AND METHODS: Activities of protein phosphatases (PPs) such as PP1, PP2A, and protein tyrosine phosphatase 1B (PTP1B) were assayed under cell-free conditions. 3-(4,5-Dimethyl-2-thiazolyl)-2,5-diphenyl-2H-tetrazolium bromide (MTT) assay, terminal deoxynucleotidyl transferase-mediated dUTP nick-end labeling (TUNEL) staining, and western blotting were carried out on the human Met5A non-malignant mesothelial cell line and NCI-H28 malignant mesothelioma cell line.
RESULTS: DPPE significantly enhanced PP2A and PTP1B activities. DPPE tended to attenuate activity of extracellular signal-regulated kinase-1 (ERK1)/ERK2, with the greater efficacy for NCI-H28 cells than that for Met5A cells. DPPE reduced NCI-H28 cell viability in a concentration (1-100 μM)-dependent manner, while it had no effect on Met5A cell viability. DPPE markedly increased TUNEL-positive cells in the NCI-H28 cell line, but otherwise induced few TUNEL-positive cells in the Met5A cell line.
CONCLUSION: The results of the present study clearly demonstrate that DPPE induces apoptosis of NCI-H28 malignant pleural mesothelioma cells. DPPE-induced enhancement of PP2A and PTP1B activities might at least in part contribute to the apoptotic effect of DPPE.

Related: Lung Cancer Mesothelioma


Sudan S, Rupasinghe HP
Quercetin-3-O-glucoside induces human DNA topoisomerase II inhibition, cell cycle arrest and apoptosis in hepatocellular carcinoma cells.
Anticancer Res. 2014; 34(4):1691-9 [PubMed] Related Publications
BACKGROUND: Dietary flavonoids have been associated with reduced risk of cancer including hepatocellular carcinoma (HCC). Quercetin-3-O-glucoside (Q3G) has been shown to possess anti-proliferative and antioxidant activities. The objectives of this study were to assess the anti-proliferative properties of Q3G in human liver cancer cells (HepG2); assess the cytotoxicity on normal primary cells; and elucidate its possible mechanism of action(s).
MATERIALS AND METHODS: Using a dose- and time-dependent study, we evaluated the antiproliferative properties of Q3G in HepG2 cells using MTS cell viability assay and lactate dehydrogenase release assay. To elucidate the mechanism of action, we performed cell-cycle analysis using flow cytometry. Cell death via apoptosis was analyzed by DNA fragmentation assay, caspase-3 induction assay and fluorescence microscopy. DNA topoisomerase II drug screening assay was performed to assess the effect of Q3G on DNA topoisomerase II.
RESULTS: Q3G treatment inhibited cell proliferation in a dose- and time-dependent manner in HepG2 cells with the blockade of the cell cycle in the S-phase. Additionally, Q3G exhibited a strong ability to inhibit DNA topoisomerase II. Furthermore, DNA fragmentation and fluorescence microscopy analysis suggested that Q3G induced apoptosis in HepG2 cells with the activation of caspase-3. Interestingly, Q3G exhibited significantly lower toxicity to normal cells (primary human and rat hepatocytes and primary lung cells) than sorafenib (p<0.05), a chemotherapy drug for hepatocellular carcinoma. The results suggest that Q3G is a potential antitumor agent against liver cancer with a possible mechanism of action via cell-cycle arrest and apoptosis. Further research should be performed to confirm these results in vivo.

Related: Liver Cancer


Valenti MT, Zanatta M, Donatelli L, et al.
Ascorbic acid induces either differentiation or apoptosis in MG-63 osteosarcoma lineage.
Anticancer Res. 2014; 34(4):1617-27 [PubMed] Related Publications
BACKGROUND/AIM: Osteosarcoma originates from mesenchymal stem cells with impaired bone differentiation. In the present study we investigated the effect of ascorbic acid (AsA) on osteogenic differentiation and apoptosis of the MG-63 osteosarcoma cell line.
MATERIALS AND METHODS: We evaluated the expression of runt-related transcription factor-2 (RUNX2) and secreted phosphoprotein 1 (SPP1) genes by real-time Polymerase Chain Reaction (PCR) and of endogenous bone morphogenetic protein-2 (BMP2) and osteocalcin proteins by immunohistochemistry. We analyzed osteoblast maturation by phosphatase alkaline synthesis and calcium deposition, and apoptosis by (TUNEL) test and Annexin staining.
RESULTS: Our results showed that RUNX2 and SPP1 gene expression was increased in cells treated with low concentrations of AsA with respect to untreated cells. At higher concentrations, AsA induced apoptosis of osteosarcoma cells, possibly with the involvement of p21.
CONCLUSION: Our findings support the ability of AsA to induce both differentiation, by affecting the target involved in early and late phases of osteogenic maturation, and apoptosis in poorly-differentiated osteosarcoma cells.

Related: Bone Cancers Osteosarcoma SPP1


Lin P, Mobasher ME, Alawi F
Acute dyskerin depletion triggers cellular senescence and renders osteosarcoma cells resistant to genotoxic stress-induced apoptosis.
Biochem Biophys Res Commun. 2014; 446(4):1268-75 [PubMed] Related Publications
Dyskerin is a conserved, nucleolar RNA-binding protein implicated in an increasing array of fundamental cellular processes. Germline mutation in the dyskerin gene (DKC1) is the cause of X-linked dyskeratosis congenita (DC). Conversely, wild-type dyskerin is overexpressed in sporadic cancers, and high-levels may be associated with poor prognosis. It was previously reported that acute loss of dyskerin function via siRNA-mediated depletion slowed the proliferation of transformed cell lines. However, the mechanisms remained unclear. Using human U2OS osteosarcoma cells, we show that siRNA-mediated dyskerin depletion induced cellular senescence as evidenced by proliferative arrest, senescence-associated heterochromatinization and a senescence-associated molecular profile. Senescence can render cells resistant to apoptosis. Conversely, chromatin relaxation can reverse the repressive effects of senescence-associated heterochromatinization on apoptosis. To this end, genotoxic stress-induced apoptosis was suppressed in dyskerin-depleted cells. In contrast, agents that induce chromatin relaxation, including histone deacetylase inhibitors and the DNA intercalator chloroquine, sensitized dyskerin-depleted cells to apoptosis. Dyskerin is a core component of the telomerase complex and plays an important role in telomere homeostasis. Defective telomere maintenance resulting in premature senescence is thought to primarily underlie the pathogenesis of X-linked DC. Since U2OS cells are telomerase-negative, this leads us to conclude that loss of dyskerin function can also induce cellular senescence via mechanisms independent of telomere shortening.

Related: Bone Cancers Osteosarcoma


Zhu X, Wang K, Zhang K, et al.
Ziyuglycoside II induces cell cycle arrest and apoptosis through activation of ROS/JNK pathway in human breast cancer cells.
Toxicol Lett. 2014; 227(1):65-73 [PubMed] Related Publications
Ziyuglycoside II, a triterpenoid saponin compound extracted from Sanguisorba officinalis L., has been reported to have a wide range of clinical applications including anti-cancer effect. In this study, the anti-proliferative effect of ziyuglycoside II in two classic human breast cancer cell lines, MCF-7 and MDA-MB-231, was extensively investigated. Our study indicated that ziyuglycoside II could effectively induce G2/M phase arrest and apoptosis in both cell lines. Cell cycle blocking was associated with the down-regulation of Cdc25C, Cdc2, cyclin A and cyclin B1 as well as the up-regulation of p21/WAF1, phospho-Cdc25C and phospho-Cdc2. Ziyuglycoside II treatment also induced reactive oxygen species (ROS) production and apoptosis by activating the extrinsic/Fas/FasL pathway as well as the intrinsic/mitochondrial pathway. More importantly, the c-Jun NH2-terminal kinase (JNK), a downstream target of ROS, was found to be a critical mediator of ziyuglycoside II-induced cell apoptosis. Further knockdown of JNK by siRNA could inhibit ziyuglycoside II-mediated apoptosis with attenuating the up-regulation of Bax and Fas/FasL as well as the down-regulation of Bcl-2. Taken together, the cell death of breast cancer cells in response to ziyuglycoside II was dependent upon cell cycle arrest and cell apoptosis via a ROS-dependent JNK activation pathway. Our findings may significantly contribute to the understanding of the anti-proliferative effect of ziyuglycoside II, in particular to breast carcinoma and provide novel insights into the potential application of such compound in breast cancer therapy.

Related: Breast Cancer


Wang H, Yu J, Zhang L, et al.
RPS27a promotes proliferation, regulates cell cycle progression and inhibits apoptosis of leukemia cells.
Biochem Biophys Res Commun. 2014; 446(4):1204-10 [PubMed] Related Publications
Ribosomal protein S27a (RPS27a) could perform extra-ribosomal functions besides imparting a role in ribosome biogenesis and post-translational modifications of proteins. The high expression level of RPS27a was reported in solid tumors, and we found that the expression level of RPS27a was up-regulated in advanced-phase chronic myeloid leukemia (CML) and acute leukemia (AL) patients. In this study, we explored the function of RPS27a in leukemia cells by using CML cell line K562 cells and its imatinib resistant cell line K562/G01 cells. It was observed that the expression level of RPS27a was high in K562 cells and even higher in K562/G01 cells. Further analysis revealed that RPS27a knockdown by shRNA in both K562 and K562G01 cells inhibited the cell viability, induced cell cycle arrest at S and G2/M phases and increased cell apoptosis induced by imatinib. Combination of shRNA with imatinib treatment could lead to more cleaved PARP and cleaved caspase-3 expression in RPS27a knockdown cells. Further, it was found that phospho-ERK(p-ERK) and BCL-2 were down-regulated and P21 up-regulated in RPS27a knockdown cells. In conclusion, RPS27a promotes proliferation, regulates cell cycle progression and inhibits apoptosis of leukemia cells. It appears that drugs targeting RPS27a combining with tyrosine kinase inhibitor (TKI) might represent a novel therapy strategy in TKI resistant CML patients.

Related: Chronic Myeloid Leukemia (CML) CML - Molecular Biology Signal Transduction Imatinib (Glivec)


Takahara K, Ii M, Inamoto T, et al.
Adipose-derived stromal cells inhibit prostate cancer cell proliferation inducing apoptosis.
Biochem Biophys Res Commun. 2014; 446(4):1102-7 [PubMed] Related Publications
Mesenchymal stem cells (MSCs) have generated a great deal of interest in the field of regenerative medicine. Adipose-derived stromal cells (AdSCs) are known to exhibit extensive proliferation potential and can undergo multilineage differentiation, sharing similar characteristics to bone marrow-derived MSCs. However, as the effect of AdSCs on tumor growth has not been studied sufficiently, we assessed the degree to which AdSCs affect the proliferation of prostate cancer (PCa) cell. Human AdSCs exerted an inhibitory effect on the proliferation of androgen-responsive (LNCaP) and androgen-nonresponsive (PC3) human PCa cells, while normal human dermal fibroblasts (NHDFs) did not, and in fact promoted PCa cell proliferation to a degree. Moreover, AdSCs induced apoptosis of LNCaP cells and PC3 cells, activating the caspase3/7 signaling pathway. cDNA microarray analysis suggested that AdSC-induced apoptosis in both LNCaP and PC3 cells was related to the TGF-β signaling pathway. Consistent with our in vitro observations, local transplantation of AdSCs delayed the growth of tumors derived from both LNCaP- and PC3-xenografts in immunodeficient mice. This is the first preclinical study to have directly demonstrated that AdSC-induced PCa cell apoptosis may occur via the TGF-β signaling pathway, irrespective of androgen-responsiveness. Since autologous AdSCs can be easily isolated from adipose tissue without any ethical concerns, we suggest that therapy with these cells could be a novel approach for patients with PCa.

Related: Prostate Cancer Signal Transduction


Han J, Tang FM, Pu D, et al.
Mechanisms underlying regulation of cell cycle and apoptosis by hnRNP B1 in human lung adenocarcinoma A549 cells.
Tumori. 2014 Jan-Feb; 100(1):102-11 [PubMed] Related Publications
AIMS AND BACKGROUND: Overexpression of heterogeneous nuclear ribonucleoprotein B1 (hnRNP B1), a nuclear RNA binding protein, has been reported to occur in early-stage lung cancer and in premalignant lesions. DNA-dependent protein kinase (DNA-PK) is known to be involved in the repair of double-strand DNA breaks. Reduced capacity to repair DNA has been associated with the risk of lung cancer.
METHODS AND STUDY DESIGN: We investigated a link between hnRNP B1 and DNA-PK and their effects on proliferation, cell cycle, and apoptosis in the human lung adenocarcinoma cell line A549.
RESULTS: We found that hnRNP B1 and DNA-PK interact with each other in a complex fashion. Reducing hnRNP B1 expression in A549 cells with the use of RNAi led to upregulation of p53 activity through upregulation of DNA-PK activity but without inducing p53 expression. Further, suppression of hnRNP B1 in A549 cells slowed cell proliferation, promoted apoptosis, and induced cell cycle arrest at the G1 stage. The presence of NU7026 reduced the arrest of cells at the G1 stage and reduced the apoptosis rate while promoting cell growth.
CONCLUSION: Taken together, our results demonstrate that by regulating DNA-PK activity, hnRNP B1 can affect p53-mediated cell cycle progression and apoptosis, resulting in greater cell survival and subsequent proliferation.

Related: Lung Cancer TP53


Chen Z, Sangwan V, Banerjee S, et al.
Triptolide sensitizes pancreatic cancer cells to TRAIL-induced activation of the death receptor pathway.
Cancer Lett. 2014; 348(1-2):156-66 [PubMed] Article available free on PMC after 28/06/2015 Related Publications
The tumor necrosis factor related apoptosis-inducing ligand (TRAIL) causes cancer cell death, but many cancers, including pancreatic cancer, are resistant to TRAIL therapy. A combination of TRAIL and the diterpene triepoxide, triptolide, is effective in inducing pancreatic cancer cell death. Triptolide increases levels of death receptor DR5 and decreases the pro-survival FLICE-like inhibitory protein (c-FLIP), which contribute to the activation of caspase-8. This combination further causes both lysosomal and mitochondrial membrane permeabilization, resulting in cell death. Our study provides a mechanism by which triptolide sensitizes TRAIL resistant cells, which may become a novel therapeutic strategy against pancreatic cancer.

Related: BID CASP8 Cancer of the Pancreas Pancreatic Cancer Signal Transduction


Foro P, Algara M, Lozano J, et al.
Relationship between radiation-induced apoptosis of T lymphocytes and chronic toxicity in patients with prostate cancer treated by radiation therapy: a prospective study.
Int J Radiat Oncol Biol Phys. 2014; 88(5):1057-63 [PubMed] Related Publications
PURPOSE: To assess the correlation of radiation-induced apoptosis in vitro of CD4 and CD8 T lymphocytes with late toxicity of prostate cancer patients treated with radiation therapy.
METHODS AND MATERIALS: 214 patients were prospectively included in the study. Peripheral blood was drawn from patients before treatment and irradiated with 8 Gy. The percentage of CD4+ and CD8+ T lymphocytes that underwent radiation-induced apoptosis was assessed by flow cytometry. Toxicity and mortality were correlated in 198 cases with pretreatment apoptosis and clinical and biological variables by use of a Cox proportional hazards model.
RESULTS: The mean percentage of CD4+ and CD8+ T lymphocyte radiation-induced apoptosis was 28.58% (±14.23) and 50.76% (±18.9), respectively. Genitourinary (GU) toxicity was experienced by 39.9% of patients, while gastrointestinal (GI) toxicity was experienced by 19.7%. The probability of development of GU toxicity was nearly doubled (hazard ratio [HR] 1.99, P=.014) in those patients in whom the percentage of in vitro radiation-induced apoptosis of CD4+ T-lymphocytes was ≤28.58%. It was also almost double in patients who received doses ≥50 Gy in 65% of the bladder volume (V65 ≥50) (HR 1.92, P=.048). No correlation was found between GI toxicity and any of the variables studied. The probability of death during follow-up, after adjustment for different variables, was 2.7 times higher in patients with a percentage of CD8+ T lymphocyte apoptosis ≤50.76% (P=.022).
CONCLUSIONS: In conclusion, our study shows, in the largest prospective cohort of prostate cancer patients undergoing radiation therapy, that in vitro radiation-induced apoptosis of CD4+ T lymphocytes assessed before radiation therapy was associated with the probability of developing chronic GU toxicity. In addition, the radiation dose received in the urinary bladder (V65 ≥50) affected the occurrence of GU toxicity. Finally, we also demonstrate that radiation-induced apoptosis of CD8+ T lymphocytes was associated with overall survival, although larger series are needed to confirm this finding.

Related: Prostate Cancer


Choi E, Kim G
Effect of artemisia species on cellular proliferation and apoptosis in human breast cancer cells via estrogen receptor-related pathway.
J Tradit Chin Med. 2013; 33(5):658-63 [PubMed] Related Publications
OBJECTIVE: To investigate the mechanism underlying the anticancer effect of Artemisia species through the inhibition of cell growth and induction of apoptosis in breast carcinoma cells.
METHODS: To evaluate the anticancer activity of methanol extracts of eight Artemisia species (Artemisia stolonifera, Artemisia selengensis, Artemisia japonica, Artemisia Montana, Artemisia capillaris, Artemisia sylvatica, Artemisia keiskeana, and Artemisia scoparia), we first investigated the proliferation of estrogen receptor (ER)-positive MCF-7 breast carcinoma cells exposed to 5 or 200 g/mL for 72 h. Apoptosis induction was assessed by an Annexin V binding assay in cells exposed to extracts at a high concentration (200 g/mL). To verify the mechanism of apoptosis, ER expression and its related signaling was investigated using an immunoblot assay under the same conditions.
RESULTS: MCF-7 cells showed the strongest antiproliferative response to the tested extracts. However, a biphasic effect was observed: the extracts inhibited proliferation at high concentrations whereas they stimulated it at low ones. ER expression was similarly modulated by the extracts. However, all of the extracts induced apoptosis at a high concentration (200 g/mL). Compared to the control level, exposure to the extracts resulted in a remarkable increase in the shift of cell populations.
CONCLUSION: The present study suggests that the tested Artemisia species exerted their anticancer effects through the induction of apoptosis via an ER-related pathway.

Related: Breast Cancer Signal Transduction


Bozok Cetintas V, Tezcanli Kaymaz B, Aktug H, et al.
Capsaicin induced apoptosis and gene expression dysregulation of human acute lymphoblastic leukemia CCRF-CEM cells.
J BUON. 2014 Jan-Mar; 19(1):183-90 [PubMed] Related Publications
PURPOSE: Capsaicin, an ingredient of red chili pepper, has possible tumorigenicity/genotoxicity properties. We aimed to determine the effects of capsaicin on the proliferation and gene expression profiles of acute lymphoblastic leukemia (ALL) CCRF-CEM cell line.
METHODS: Cell viability and IC50 dose was determined by WST cytotoxicity assay. qRT-PCR, immunohistochemical staining and western blot methods were used to determine target genes' expression levels. Apoptosis was evaluated by measuring the caspase-3 activity.
RESULTS: Capsaicin inhibited the proliferation of CCRFCEM cells in a dose-dependent manner. Increased mRNA expressions of caspase gene family members, activated caspase-3 and decreased mRNA and protein expression of BCL-2 gene indicated apoptotic response to capsaicin. Moreover capsaicin treatment suppressed significantly the expression of the key cell signaling pathways of KRAS, AKT, GAB2, PTPN11, BRAF, INPP5D, MAPK7.
CONCLUSION: Capsaicin induces apoptosis in CCRF-CEM cells and this response is associated with downregulation of cell signaling pathways.

Related: Acute Lymphocytic Leukemia (ALL) Signal Transduction


Palmeira dos Santos C, Pereira GJ, Barbosa CM, et al.
Comparative study of autophagy inhibition by 3MA and CQ on Cytarabine‑induced death of leukaemia cells.
J Cancer Res Clin Oncol. 2014; 140(6):909-20 [PubMed] Related Publications
BACKGROUND: As the molecular mechanisms of Cytarabine,one of the most important drugs used in the leukaemia’s treatment, are only partially understood and the role of autophagy on leukaemia development and treatment is only recently being investigated, in this study, by using Chloroquine (CQ) and 3-methyladenine (3MA) as autophagy inhibitors, we aim to evaluate the contribution of an autophagic mechanism to Cytarabine (AraC)-induced death of HL60 leukaemia cells.
METHODS: Trypan blue exclusion and AnnexinV/PI assays were used to evaluate HL60 cell death under AraC treatment in the presence or absence of 3MA and CQ. Western blotting and immunofluorescence experiments were performed to show the involvement of apoptosis and autophagy protein expressions. Phenotypic characterization of HL60-treated cells was performed by using immunophenotyping. Clonogenic assays were applied to analyse clonal function of HL60-treated cells.
RESULTS: We observed that although autophagy inhibition by 3MA, but not CQ, increased the death of HL60 AraC cells after 24 h of treatment, no significant differences between AraC and AraC + 3MA-treated groups were observed by using clonogenic assay. In addition, increased number of immature (CD34(+)/CD38(−)Lin(−/low)) HL60 cells was found in AraC and AraC-3MA groups when compared with control untreated cells.
CONCLUSIONS: Although AraC anti-leukaemia effects could be potentiated by 3MA autophagy inhibition after 24 h of exposure, leukaemia cell resistance, the main causes of treatment failure, is also promoted by autophagy initial stage impairment by 3MA, denoting the complex role of autophagy in leukaemia cells’ response to chemotherapy.

Related: Cytarabine Leukemia RARA gene


Cheng HY, Ko FH
Studying the enhancement of programmed cell death by combined AG1024 and paclitaxel in a model of chronic myelogenous leukemia.
Life Sci. 2014; 102(2):118-26 [PubMed] Related Publications
AIMS: Chronic myelogenous leukemia is a clonal malignancy of the pluripotent hematopoietic stem cells that is characterized by the uncontrolled proliferation and expansion of myeloid progenitors. Myeloid progenitors express the fusion oncogene BCR-ABL, which has uncontrollable activity in malignant cells and prevents the cell apoptosis caused by some antineoplastic agents, such as paclitaxel. Targeting these abnormalities by blocking the tyrosine kinase enzymes of BCR-ABL is a promising approach for chronic myelogenous leukemia therapy.
MAIN METHODS: Conventional Liu's staining is an auxiliary technique used in microscopy to enhance the contrast in microscopic images, aiding the observation of cell morphology. The MTT assay, flow cytometry of the sub-G1 analysis and the TUNEL assay were applied to estimate the apoptosis levels. RT-PCR and western blot methods were used to evaluate the key molecules conferring anti-cell-death properties.
KEY FINDINGS: The effects of the tyrosine kinase inhibitor AG1024 were evaluated with regard to the regulation of BCR-ABL expression, inhibition of cell proliferation, and enhanced paclitaxel-induced apoptosis in BCR-ABL-expressing K562 cell lines. AG1024 downregulated the expression of BCR-ABL and anti-apoptosis factors, such as Bcl-2 and Bcl-xL, which were present in K562 cells. Moreover, the combination of AG1024 with paclitaxel inhibited cell proliferation and enhanced paclitaxel-induced apoptosis within 24h.
SIGNIFICANCE: In summary, the present study shows that the combination of AG1024 with paclitaxel inhibited model cancer cell proliferation, suggesting a new use of paclitaxel-based chemotherapy for cancer control.

Related: Chronic Myeloid Leukemia (CML) CML - Molecular Biology Paclitaxel


Jazirehi AR, Kurdistani SK, Economou JS
Histone deacetylase inhibitor sensitizes apoptosis-resistant melanomas to cytotoxic human T lymphocytes through regulation of TRAIL/DR5 pathway.
J Immunol. 2014; 192(8):3981-9 [PubMed] Related Publications
Modern immune therapies (PD-1/PD-L1 and CTLA-4 checkpoints blockade and adoptive cell transfer) have remarkably improved the response rates of metastatic melanoma. These modalities rely on the killing potential of CTL as proximal mediator of antimelanoma responses. Mechanisms of tumor resistance to and the predominant cytotoxic pathway(s) used by melanoma-reactive CTL are important outcome determinants. We hypothesized that downmodulation of death receptors (DRs) in addition to aberrant apoptotic signaling might confer resistance to death signals delivered by CTL. To test these two hypotheses, we used an in vitro model of MART CTL-resistant melanoma sublines. TCR-transgenic and patient-derived CTLs used the TRAIL cytotoxic pathway through DR5. Furthermore, recombinant human TRAIL and drozitumab (anti-DR5 agonistic mAb) were used to explicitly verify the contribution of the DR5/TRAIL pathway in killing melanomas. CTL resistance was due to DR5 downregulation and an inverted ratio of pro- to antiapoptotic molecules, both of which were reversed by the histone deacetylase inhibitor suberoylanilide hydroxanic acid. Apoptosis negative (c-IAP-2 and Bcl-xL) and positive (DR5) regulators were potential incriminators partly regulating CTL sensitivity. These preclinical findings suggest that exposure to this chromatin remodeling drug of immune-resistant melanomas can skew toward an intracellular proapoptotic milieu, increase DR expression, and overcome acquired immune resistance.

Related: Melanoma Signal Transduction


Wang S, Bao Z, Liang QM, et al.
Octreotide stimulates somatostatin receptor-induced apoptosis of SW480 colon cancer cells by activation of glycogen synthase kinase-3β, A Wnt/β-catenin pathway modulator.
Hepatogastroenterology. 2013; 60(127):1639-46 [PubMed] Related Publications
BACKGROUND/AIMS: Peptide hormone somatostatin and its receptors (SSTRs) have a wide range of physiological functions and play a role in the treatment of numerous human diseases, including colorectal cancer. Octreotide, a somatostatin-analog peptide, inhibits growth of colonic cancer SW480 cells through Wnt/β-catenin pathway modulation. However, the specific octreotide-stimulating SSTR subtypes and the signal-transduction mechanism responsible for the negative regulation of Wnt/β-catenin pathway by octreotide have not been fully elucidated.
METHODOLOGY: Octreotide-induced apoptosis in SW480 colon cancer cells mediated by SSTR2,SSTR5-dependent regulation of the Wnt/β-catenin pathway components GSK-3β and β-catenin was investigated. Cell apoptosis of SW480 cells was measured by apoptosis-DNA ladder assay. SSTR1, SSTR2, SSTR3, SSTR4, and SSTR5 mRNA expression levels were confirmed by RT-PCR; β-catenin, TCF-4, cyclin D1, c-Myc, and GSK-3β protein levels were examined by Western blot. The distribution of β-catenin in the cell was analyzed with immunocytochemistry.
RESULTS: Octreotide treatment increased SSTR2,SSTR5-induced apoptosis of SW480 colon cancer cells, promoted the plasma membrane accumulation of β-catenin, inactivated T-cell factor-dependent transcription, and downregulated Wnt target genes cyclin D1 and c-Myc. Further, octreotide treatment mediated the activation of GSK-3.
CONCLUSIONS: These preliminary findings showed the negative regulation of the Wnt/β-catenin pathway by peptide hormone G protein-coupled receptors SSTRs.


Duan L, Hao X, Liu Z, et al.
MiR-129-5p is down-regulated and involved in the growth, apoptosis and migration of medullary thyroid carcinoma cells through targeting RET.
FEBS Lett. 2014; 588(9):1644-51 [PubMed] Related Publications
Dysregulation of the REarranged during Transfection proto-oncogene (RET) pathway and microRNA (miRNAs) are crucial for the development of medullary thyroid carcinomas (MTC). Here we demonstrate that miR-129-5p is down-regulated in MTC tissues and cell lines and inhibits RET expression by directly binding its 3' untranslated regions. Ectopic expression of miR-129-5p significantly decreases cell growth, induces apoptosis and suppresses migration ability in MTC cells through decreasing the phosphorylated AKT, thus functioning as a tumor suppressor. These findings give new clues for understanding MTC carcinogenesis and may help in developing a therapeutic approach for the treatment of RET-activated MTC.

Related: Thyroid Cancer RET


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