"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)
Web Resources: Apoptosis
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Web Resources: Apoptosis (2 links)
This list of publications is regularly updated (Source: PubMed).
Anticancer activity of two ruthenium(II)-DMSO-chalcone complexes: Comparison of cytotoxic, pro-apoptotic and antimetastatic potential.
J BUON. 2016 Mar-Apr; 21(2):482-90 [PubMed] Related Publications
METHODS: Characterization of anticancer activity of the investigated ruthenium complexes 1 and 2 included analysis of cytotoxicity by MTT assay. Cell cycle phase disruption of HeLa cells treated with complexes 1 and 2 was analyzed by flow cytometry after propidium iodide (PI) staining. Annexin V-FITC/PI double staining and further flow cytometry analysis and acridine orange (AO)/ethidium bromide (EB) double staining and fluorescent microscopy were used to determine the apoptotic potential of the investigated ruthenium complexes. The inhibitory effect on gelatinases (MMP-2 and MMP-9) as an indication of possible antimetastatic potential was also analyzed using gelatine zymography.
RESULTS: The 50% cell growth inhibition (IC50) values of the investigated complexes ranged between 22.9 and 76.8 μM, with complex 2 being more cytotoxic. Both complexes induced G2 phase cell cycle arrest and apoptosis in HeLa cells. Inhibitory effect of complex 2 on MMP-2 activity was detected.
CONCLUSIONS: This work revealed the potential of the investigated Ru(II)-DMSO-chalcone complexes as anticancer agents with cytotoxic and pro-apoptotic activity and indicated complex 2 as leading compound for further chemical modifications and anticancer research.
The combination use of 1-O-acetylbritannilactone (ABL) and gemcitabine inhibits cell growth and induces cell apoptosis in lung adenocarcinoma cells.
Pharmazie. 2016; 71(4):213-7 [PubMed] Related Publications
Assessment of pathological response to neoadjuvant chemotherapy in locally advanced breast cancer using the Miller-Payne system and TUNEL.
Malays J Pathol. 2016; 38(1):25-32 [PubMed] Related Publications
MATERIALS AND METHOD: A cross-sectional analytical retrospective study was conducted on tissue of LABC diagnosed between 2010 and 2014 at the Department of Anatomical Pathology, Faculty of Medicine, Universitas Indonesia Cipto Mangunkusumo Hospital and Division of Surgical Oncology, Cipto Mangunkusumo Hospital. Biopsy and resection specimens were compared to evaluate reduction in cellularity, which were subsequently categorized into stages of Miller-Payne (MP) classification. The resection specimens were stained with TUNEL and the percentage of apoptosis was calculated. Reduction in cellularity between biopsy and mastectomy specimens with TUNEL staining is evaluated as a modification of the MP method.
RESULTS: We found no association between clinical responses with percentage of apoptosis, MP pathological responses and modified MP. There was a correlation between the dead cell evaluated by MP and by modified MP (p=0.000).
CONCLUSION: Modified MP increases the degree or grading of pathological responses, but it does not improve the correlation with clinical response.
Myricetin exhibits anti-glioma potential by inducing mitochondrial-mediated apoptosis, cell cycle arrest, inhibition of cell migration and ROS generation.
J BUON. 2016 Jan-Feb; 21(1):182-90 [PubMed] Related Publications
METHODS: Cell viability of human glioma cells after myricetin treatment was assessed by MTT assay. Phase-contrast and confocal fluorescence microscopies were used to assess the morphological changes that occured in these cells following myricetin treatment. Flow cytometry using propidium iodide (PI) and Annexin-V FITC as probes was employed to evaluate the effects on cell cycle arrest and apoptosis induction, respectively. The effect of myricetin on intracellular ROS production was measured by flow cytometry with a fluorescent probe CM-DCFH2-DA.
RESULTS: Myricetin induced a dose-dependent as well as time-dependent growth inhibitory effect in U251 human glioma cells. Myricetin treatment resulted in U251 cells detachment from adjacent cells making clusters of cells floating in the medium. Detached cells had irregular shape and incapable to maintain their membranes intact. Apoptotic cell death was induced by myricetin treatment as witnessed by fluorescence microscopy. The percentage of early and late apoptotic cells increased from 0.41% and 8.2% to 23.1% and 10.2%, 25.2% and 19.4%, to finally 36.2% and 28.4% after treatment with 15 μM, 60 μM and 120 μM of myricetin, respectively. We also observed a dose-dependent increase in Bax and Bad levels and a dose-dependent decrease in Bcl-2 and Bcl-xl expression levels following myricetin treatment. Cell cycle arrest in G2/M phase of the cell cycle was also induced by the drug treatment. A concentration-dependent ROS generation was also witnessed and a 3-fold increase of ROS production was seen after 60 μM myricetin treatment.
CONCLUSION: Myricetin exerts anticancer effects in U251 human glioma cells by inducing mitochondrial-mediated apoptosis, G2/M phase cell cycle arrest, ROS generation and inhibition of cell migration.
Arctigenin induces apoptosis in colon cancer cells through ROS/p38MAPK pathway.
J BUON. 2016 Jan-Feb; 21(1):87-94 [PubMed] Related Publications
METHODS: Cell growth inhibition was assessed by MTT and LDH assays. Flow cytometric analysis was performed to determine cell arrest in the cell cycle phase and apoptosis. Furthermore, to confirm the apoptotic activity of arctigenin, caspase-9 and -3 activities analysis was performed. The levels of reactive oxygen species (ROS) and p38 mitogen activated protein kinase (MAPK) were investigated to determine their role in inducing apoptosis in arctigenin-treated HT-29 colon cancer cell line.
RESULTS: MTT and LDH results demonstrated significant cell growth inhibitory effect of arctigenin on HT-29 cells in a dose-dependent manner. Furthermore, increase in cell number arrested at G2/M phase was observed in flow cytometric analysis upon arctigenin treatment. In addition, arctigenin increased the apoptotic ratio in a dose-dependent manner. The involvement of intrinsic apoptotic pathway was indicated by the activation of caspase-9 and -3. Moreover, increased ROS production, activation of p38 MAPK and changes in mitochondrial membrane potential (ΔΨm) also revealed the role of intrinsic apoptotic signaling pathway in cell growth inhibition after arctigenin exposure.
CONCLUSION: Arctigenin induces apoptosis in HT-29 colon cancer cells by regulating ROS and p38 MAPK pathways.
Influence of Tanshinone IIA on the Apoptosis of Human Esophageal Ec-109 Cells.
Nat Prod Commun. 2016; 11(1):17-9 [PubMed] Related Publications
Influence of Photodynamic Therapy on Apoptosis and Invasion of Human Cholangiocarcinoma QBC939 Cell Line.
Chin Med Sci J. 2015; 30(4):252-9 [PubMed] Related Publications
METHODS: In vitro cultured cholangiocarcinoma QBC939 cell line was exposed to 2, 4, 6, 8, 10, 12, and 14 μg/ml HPD with 5, 10, and 15 J/cm2 light intensity, respectively. The optical density at 450 nm of the QBC939 cells was measured by CCK8 assay and its growth inhibition ratio was calculated. Flow cytometry and transwell migration assay were applied to detect cell apoptosis and invasion respectively. RT-PCR and immunocytochemistry analyses were used to detect expressions of vascular endothelial growth factor-C (VEGF-C), cyclooxygenase-2 (COX-2), and proliferating cell nuclear antigen (PCNA). Enzyme-linked immunosorbent assay (ELISA) was carried out to examine the secretion of VEGF-C and COX-2 in QBC939 cells.
RESULTS: Exposure to HPD-PDT can significantly suppress the growth of QBC939 cells (all P<0.05). HPD-PDT can promote apoptosis of QBC939 cells at the early stage. When the concentration of HPD was 2 μg/ml and light irradiation was 5 J/cm2, HPD-PDT had no obvious inhibitory effect on QBC939 cell growth, but can obviously inhibit cell invasion, and significant difference was observed between the HPD-PDT and control groups (P<0.01). The HPD-PDT can reduce the mRNA and protein expressions of VEGF-C, COX-2, and PCNA, and decrease the secretion of VEGF-C and COX-2 in QBC939 cells.
CONCLUSION: PDT could promote apoptosis and inhibit growth and invasion of cholangiocarcinoma cells QBC939 in vitro.
Rapamycin-Mediated mTOR Inhibition Reverses Drug Resistance to Adriamycin in Colon Cancer Cells.
Hepatogastroenterology. 2015; 62(140):880-6 [PubMed] Related Publications
METHODOLOGY: LoVo/Adr cells were designated accordingly into ADR group, Rapamycin (RAPA) group, ADR plus RAPA, and control group in main observations. Autophage, cell death and mdr1 were examined.
RESULTS: IC50 value of ADR in LoVo/Adr was significantly decreased in response to RAPA (P < 0.05). Autophagy rate of LoVo/Adr cells was higher in the ADR or RAPA-alone group than in control (p < 0.05), while ADR/RAPA combination has significantly increased autophagy rate compared to ADR or RAPA alone (p < 0.05). Compared with controls, apoptosis rate in the RAPA group had no difference (p > 0.05); whereas there was significant difference in ADR group (p < 0.05). Furthermore, apoptosis rate was significantly different in combined RAPA/ADR compared to ADR (p < 0.05). Expression of mRNA and protein P-gp level of mdr 1 gene in LoVo/Adr cells were significantly decreased under RAPA-treated groups at 25 µmol/L and 50 µmol/L (p < 0.05).
CONCLUSION: This study has indicated that the inhibition of the mTOR pathway reverses multidrug resistance in colorectal cancer cells, which is associated with increased autophagy, apoptosis and reduced mdr1 gene expression in drug-resistant cells treated with Adriamycin.
Novel Molecular Regulators of Tumor Necrosis Factor-Related Apoptosis-Inducing Ligand (TRAIL)-Induced Apoptosis in NSCLC Cells.
Clin Lab. 2015; 61(12):1855-63 [PubMed] Related Publications
METHODS: The TRAIL-sensitive NSCLC cell line NCI-H358 and a TRAIL-resistant cell line A549 were treated with rmhTRAIL for 24 hours. Then cell viability were measured by MTT assay, meanwhile cell cycle and apoptosis were measured by flow cytometry. Furthermore, mass spectrometry (LC-MS/MS) was used to identify the difference in the protein expression profiles. Finally, real-time PCR was performed to detect the mRNA expression of TRAIL receptors and apoptotic related proteins.
RESULTS: These results confirmed that NCI-H358 cells were sensitive to TRAIL, whereas A549 cells were resistant. Both mRNA and protein levels of voltage-dependent anion-selective channel proteinl (VDAC1), caspase9 (CASP9), and cytochrome c1 (CYC1) were upregulated in H358 cells but downregulated in A549 cells, whereas antiapoptotic protein BAG-2 was downregulated. In addition, TRAIL also causes DR5 low expression in A549 cells.
CONCLUSIONS: These results indicate that rmhTRAIL had different anti-tumor activity in different NSCLC cell lines. Downregulation of VDAC1, CYC1, CASP9, and upregulation of BAG-2 might be associated with underlying TRAIL-resistance mechanisms. These findings motivated further studies to explore new therapeutic strategy overcoming TRAIL-resistance of NSCLC cells through modulating dysregulation of the proteins above.
5-Aza-2'-Deoxycytidine and CDDP Synergistically Induce Apoptosis in Renal Carcinoma Cells via Enhancing the APAF-1 Activity.
Clin Lab. 2015; 61(12):1821-30 [PubMed] Related Publications
METHODS: We evaluated the DNA demethylation by DAC in human renal carcinoma cells and determined the synergism of the demethylation with the toxicity of Cisplatin (CDDP), which is a commonly utilized anti-tumor agent for renal carcinoma.
RESULTS: It was demonstrated that DAC promoted a significant global genomic demethylation and improved APAF-1 expression at both mRNA and protein levels. The DAC treatment deteriorated the CDDP-induced viability decreasing Caki or ACHN cells and synergized the apoptosis induction of CDDP in ACHN cells. The treatment with both DAC and CDDP promoted a significantly higher level of renal carcinoma cell apoptosis than singular DAC or CDDP treatment. The APAF-1 knockdown significantly inhibited the synergism of DAC with the CDDP-induced apoptosis in ACHN cells.
CONCLUSIONS: The present study confirmed that DAC demethylated the CpGs, particularly APAF-1 in renal carcinoma cells, and that the demethylation synergized the cytotoxity of CDDP in renal carcinoma cells via enhancing the CDDP-induced apoptosis.
MiR-26b inhibits melanoma cell proliferation and enhances apoptosis by suppressing TRAF5-mediated MAPK activation.
Biochem Biophys Res Commun. 2016; 471(3):361-7 [PubMed] Related Publications
Exploitation of the Apoptosis-Primed State of MYCN-Amplified Neuroblastoma to Develop a Potent and Specific Targeted Therapy Combination.
Cancer Cell. 2016; 29(2):159-72 [PubMed] Free Access to Full Article Related Publications
The small molecule survivin inhibitor YM155 may be an effective treatment modality for colon cancer through increasing apoptosis.
Biochem Biophys Res Commun. 2016; 471(2):309-14 [PubMed] Related Publications
Anticancer effects of bishydroxycoumarin are mediated through apoptosis induction, cell migration inhibition and cell cycle arrest in human glioma cells.
J BUON. 2015 Nov-Dec; 20(6):1592-600 [PubMed] Related Publications
METHODS: Three cells were used in the experiments. MTT and LDH assays were used to assess the cytotoxic effects of BHC while an in vitro wound healing assay was used to study the effect of BHC on cell migration. Fluorescence microscopy and annexin V-FITC assay were used to study the cellular morphology and apoptotic effects while flow cytometry in combination with propidium iodide (PI) were used to study cell cycle arrest induced by BHC.
RESULTS: BHC induced substantial and dose-dependent cytotoxic effects against all three cell lines with U87MG cell line being most susceptible. BHC also inhibited cell migration and induced characteristic morphological changes including chromatin condensation, nuclear shrinkage which increased with increasing dose of BHC. The apoptotic cell population (both early and late apoptotic cells) increased with increasing dose of BHC which also induced substantial G0/G1 cell cycle growth arrest in U87MG cells.
CONCLUSION: This study provides help to elucidate the translational potential of the in vitro results to be used for further in vivo studies on human glioma using animal or human subjects. The mechanistic pathway studied in this report could be helpful in explaining the mode of action of these classes of natural products.
Inhibitory effect of Aphidicolin - a tetracyclic diterpene - on the proliferation and apoptotic induction in human cervical cancer (HeLa) cells.
J BUON. 2015 Nov-Dec; 20(6):1480-6 [PubMed] Related Publications
METHODS: Flow cytometry was performed to detect alterations in the mitochondrial membrane potential loss (ΔΨm) after aphidicolin treatment. Cell viability was assessed by the MTT assay while the apoptotic effects of the compound were examined by fluorescence microscopy and flow cytometry.
RESULTS: Aphidicolin induced dose-dependent as well as time-dependent cytotoxic effects in HeLa cells. Chromatin condensation and formation of apoptotic bodies were observed by Hoechst 33258 staining after drug treatment. Aphidicolin induced both early and late apoptosis in HeLa cells which were correlated with strong concentration of the compound. ΔΨm was also observed following aphidicolin treatment at varying doses.
CONCLUSION: Aphidicolin is a potent antitumor and apoptotic agent against human cervical carcinoma and its effects are mediated via chromatin condensation and mitochondrial membrane potential loss.
Polyphosphate Derived from Lactobacillus brevis Inhibits Colon Cancer Progression Through Induction of Cell Apoptosis.
Anticancer Res. 2016; 36(2):591-8 [PubMed] Related Publications
Potential Dual Role of Activating Transcription Factor 3 in Colorectal Cancer.
Anticancer Res. 2016; 36(2):509-16 [PubMed] Related Publications
MATERIALS AND METHODS: ATF3 was overexpressed in human colorectal cancer cells and the effects of ATF3 on apoptosis, cell cycle, cell migration and epithelial mesenchymal transition (EMT) were investigated. B-cell lymphoma-2 (Bcl-2) promoter was cloned and used for luciferase assay in cells transfected with control or ATF3 expression vector.
RESULTS: ATF3 down-regulated the expression of Bcl-2 and promoter activity of the Bcl-2 gene. ATF3 increased collective cell migration and expression of cluster of differentiation 44 (CD44) and decreased retinoblastoma (Rb) expression. In addition, ATF3 down-regulated EMT-inducing transcription factors and β-catenin.
CONCLUSION: ATF3 may play a dichotomous role in apoptosis and metastasis in human colorectal cancer cells.
A monoclonal antibody against KCNK9 K(+) channel extracellular domain inhibits tumour growth and metastasis.
Nat Commun. 2016; 7:10339 [PubMed] Free Access to Full Article Related Publications
Amygdalin delays cell cycle progression and blocks growth of prostate cancer cells in vitro.
Life Sci. 2016; 147:137-42 [PubMed] Related Publications
MAIN METHODS: LNCaP (castration-sensitive), DU-145 and PC3 cells (castration-resistant) were exposed to different concentrations of amygdalin for 24h or 2weeks. Cell growth was measured by the MTT test, clonal formation by the clonogenic assay. Flow cytometry served to investigate apoptosis and cell cycle phases. Cell cycle regulating proteins and the mTOR-akt signaling axis were analyzed by western blotting.
KEY FINDINGS: Amygdalin dose-dependently diminished tumor cell growth with maximum effects at 10mg/ml. Apoptosis of PC3 and LNCaP but not of DU-145 cells was reduced, whereas colony formation was suppressed in all cell lines. A decrease in the number of G2/M- and S-phase cells along with an elevated number of G0/G1-phase cells was recorded. The cell cycle proteins cdk 1, cdk 2 and cdk 4 as well as cyclin A, cyclin B and cyclin D3 were modulated by amygdalin after both 24h and 2weeks. Distinct effects on p19 and p27 expression and on Akt, Rictor and Raptor activation became evident only after 2weeks.
SIGNIFICANCE: Amygdalin exhibits significant antitumor activity in both castration-sensitive and castration-resistant PCa cell lines and merits further evaluation for therapeutic purposes.
Cancer-associated fibroblasts attenuate Cisplatin-induced apoptosis in ovarian cancer cells by promoting STAT3 signaling.
Biochem Biophys Res Commun. 2016; 470(4):947-54 [PubMed] Related Publications
Antiproliferation and Apoptosis Induction in Colorectal Cancer Cells by Goniothalamin.
J Med Assoc Thai. 2015; 98 Suppl 9:S146-51 [PubMed] Related Publications
BACKGROUND: Colorectal cancer is the third of the twentieth most commonly diagnosed cancer. Different types of colorectal cancer cells differ in genotype and characteristics leading to different responses to anticancer drugs. Therefore, finding new anticancer compound for the colorectal cancer cells is necessary.
MATERIAL AND METHOD: Antiproliferative response of goniothalamin on three colorectal cancer cell lines including Colo 205, SW480, and LoVo were determined by MTT assay. The antiproliferative response at different time and dose was also observed. Apoptosis induction by goniothalamin was observed in all three cell-lines via morphological changes and nuclear condensation by Hoechst33342 staining.
RESULTS: Goniothalamin showed different antiproliferative response on Colo 205, SW480, and Lo Vo cells at the IC50 value is 9.86 ± 0.38 µM, 22.00 ± 4.40 µM, and 65.25 ± 1.85 µM respectively. In addition, the antiproliferative response of goniothalamin was a time- and dose-dependent manner Apoptosis morphological changes and nuclear condensation were clearly observed in Colo 205, SW480 and LoVo cells treated with 10 µM, 25 µM, and 50 µM goniothalamin, respectively.
CONCLUSION: Goniothalamin showed antiproliferation and apoptosis induction in colorectal cancer cells with different sensitivity depending on cell type. Investigation of mechanisms underlying apoptosis and its potential use for colorectal cancer treatment should be further studied.
Granzyme B-based cytolytic fusion protein targeting EpCAM specifically kills triple negative breast cancer cells in vitro and inhibits tumor growth in a subcutaneous mouse tumor model.
Cancer Lett. 2016; 372(2):201-9 [PubMed] Related Publications
SKF-96365 activates cytoprotective autophagy to delay apoptosis in colorectal cancer cells through inhibition of the calcium/CaMKIIγ/AKT-mediated pathway.
Cancer Lett. 2016; 372(2):226-38 [PubMed] Related Publications
Resveratrol and the mitochondria: From triggering the intrinsic apoptotic pathway to inducing mitochondrial biogenesis, a mechanistic view.
Biochim Biophys Acta. 2016; 1860(4):727-45 [PubMed] Related Publications
SCOPE OF REVIEW: This paper aims to review the molecular pathways underlying the beneficial effects of resveratrol on mitochondrial structure and functions. In addition, we discuss the chemistry and main sources of resveratrol.
MAJOR CONCLUSIONS: Resveratrol represents the promising effects on mitochondria in different experimental models. However, there are several reports on the detrimental effects elicited by resveratrol on mitochondria.
GENERAL SIGNIFICANCE: An understanding of the chemistry and source of resveratrol, its bioavailability and the promising effects on mitochondria brings a new hope to therapy of mitochondrial dysfunction-related diseases.
Synergistic anticancer activity of dietary tea polyphenols and bleomycin hydrochloride in human cervical cancer cell: Caspase-dependent and independent apoptotic pathways.
Chem Biol Interact. 2016; 247:1-10 [PubMed] Related Publications
Identification of novel alternative splice variants of the BCL2L12 gene in human cancer cells using next-generation sequencing methodology.
Cancer Lett. 2016; 373(1):119-29 [PubMed] Related Publications
Tumor necrosis factor-related apoptosis-inducing ligand (TRAIL) activates caspases in human prostate cancer cells through sigma 1 receptor.
Biochem Biophys Res Commun. 2016; 470(2):319-23 [PubMed] Related Publications
Inhibition of glucose transporter 1 induces apoptosis and sensitizes multiple myeloma cells to conventional chemotherapeutic agents.
Leuk Res. 2016; 41:103-10 [PubMed] Related Publications
Short Telomeres in Key Tissues Initiate Local and Systemic Aging in Zebrafish.
PLoS Genet. 2016; 12(1):e1005798 [PubMed] Free Access to Full Article Related Publications
Biological evaluation of 2-arylidene-4, 7-dimethyl indan-1-one (FXY-1): a novel Akt inhibitor with potent activity in lung cancer.
Cancer Chemother Pharmacol. 2016; 77(2):393-404 [PubMed] Related Publications
METHODS: FXY-1 efficacy was assessed by standard anticancer screening in NCI-H 460, A549, NCI-H 1975 and NCI-H 2170 cells. Initial molecular docking analysis was performed to check the interaction of compound to Akt enzyme. Anti-proliferation, anti-metastatic and transendothelial cell migration were performed to check efficacy of the drug. Western blot analysis was performed to understand the regulation of pro-apoptotic and anti-apoptotic proteins by the compound. The effect of FXY-1 on caspase induction and Akt phosphorylation were checked using Western blot analysis. Flow cytometry was used to reveal the cell cycle changes and apoptosis-inducing properties of FXY-1 in the lung cancer cells. In-vitro Akt inhibition property of the compound was studied using a fluorescence-based, coupled-enzyme reaction. The in-vivo efficacy of the compound was determined using a mouse xenograft model.
RESULTS: Our molecular docking analysis reveals higher interaction of FXY-1 with Akt. FXY-1 depicted anti-proliferative and pro-apoptotic activity with higher therapeutic window in-vitro in NCI-H 460 and A549 cells. The compound treatment to lung cancer cells resulted in induction of DNA fragmentation, inhibition of transendothelial migration, caspase activation and poly (ADP-ribose) polymerase (PARP) cleavage. FXY-1 treatment resulted in G 0/G 1 arrest in both cell lines at lower concentrations, but led to apoptosis at higher doses. Western blot analysis revealed dephosphorylation of Akt (Ser 473) with activation of p53, Bax, Bak, Bid and reduction in Bcl-2 and Bcl-xL levels. Further mechanistic investigation showed that FXY-1 activity was facilitated through an allosteric inhibition of Akt enzyme. FXY-1 treatment significantly reduced the tumor growth and pAkt levels in mouse xenograft exhibiting the in-vivo efficacy in the compound.
CONCLUSION: Collectively, our results suggest DNA damage-mediated activation by FXY-1 in lung cancer cells leading to extensive apoptosis through the mitochondrial pathway.