Involvement of Bcl-2 family, cytochrome c and caspase 3 in induction of apoptosis by beauvericin in human non-small cell lung cancer cells.
Beauvericin (BEA), a cyclic hexadepsipeptide from Codyceps cicadae, possesses anti-convulsion, anti-arrhythmia, sedation, and anti-tumor activities. It has been reported that BEA induces apoptosis in several cancer cell lines. However, the molecular mechanism underlying the BEA-induced apoptotic process is not yet clearly understood. In the present study, the intracellular signaling pathways of BEA-induced apoptosis in human non-small cell lung cancer (NSCLC) A549 cells were investigated using morphological analysis and terminal deoxynucleotidyl transferase dUTP nick-end labeling (TUNEL) technique. In this study, BEA-induced apoptosis in human NSCLC A549 cells demonstrated a BEA concentration- and treatment time-dependent manner. This BEA-induced apoptosis in human NSCLC A549 cells was also accompanied by the up-regulation of Bax, Bak, and p-Bad and down-regulation of p-Bcl-2, but no effect on the levels of Bcl-X(L) or Bad proteins. Moreover, the BEA treatment resulted in a significant reduction of mitochondrial membrane potential, increase in the release of mitochondrial cytochrome c (cyt c), and activation of caspase 3. Furthermore, treatment with caspase 3 inhibitor (z-DEVD-fmk) was capable to prevent the BEA-induced caspase 3 activity and cell death. These results clearly demonstrate that the induction of apoptosis by BEA involves multiple cellular/molecular pathways and strongly suggest that pro- and anti-apoptotic Bcl-2 family proteins, mitochondrial membrane potential, mitochondrial cyt c, and caspase 3, they all participate in BEA-induced apoptotic process in human NSCLC A549 cells.
Lin
Hen-I
HI
School of Medicine, Fu Jen Catholic University, 510, Chung-Cheng Road, Hsin-Chuang, Taipei Hsien 242, Taiwan.
Lee
Yih-Jing
YJ
Chen
Bing-Fang
BF
Tsai
Meng-Chao
MC
Lu
Jen-Lin
JL
Chou
Cheng-Jen
CJ
Jow
Guey-Mei
GM
D000970:Antineoplastic Agents / Q000494:pharmacology*; D017209:Apoptosis; D002289:Carcinoma, Non-Small-Cell Lung; D053148:Caspase 3; D020169:Caspases / Q000378:metabolism; D045744:Cell Line, Tumor; D002470:Cell Survival / Q000187:drug effects; D045304:Cytochromes c / Q000378:metabolism; D053938:DNA Fragmentation; D047630:Depsipeptides / Q000494:pharmacology*; D006801:Humans; D020287:In Situ Nick-End Labeling; D008175:Lung Neoplasms; D008564:Membrane Potentials / Q000187:drug effects; D008928:Mitochondria / Q000187:drug effects / Q000378:metabolism / Q000502:physiology; D019253:Proto-Oncogene Proteins c-bcl-2 / Q000378:metabolism
D000970:Antineoplastic Agents; D047630:Depsipeptides; D019253:Proto-Oncogene Proteins c-bcl-2; C004456:beauvericin; D045304:Cytochromes c; C505407:CASP3 protein, human; D053148:Caspase 3; D020169:Caspases