Involvement of Bcl-2 family, cytochrome c and caspase 3 in induction of apoptosis by beauvericin in human non-small cell lung cancer cells.

Abstract

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.

• Authors: Hen-I Lin, Yih-Jing Lee, Bing-Fang Chen, Meng-Chao Tsai, Jen-Lin Lu, Cheng-Jen Chou, Guey-Mei Jow
• Journal: Cancer letters (Cancer Lett) Vol. 230 Issue 2 Pg. 248-59 (Dec 18 2005) ISSN: 0304-3835 [Print] Ireland
• PMID: 16297711 (Publication Type: Journal Article, Research Support, Non-U.S. Gov't)

Chemical References

• Antineoplastic Agents
• Depsipeptides
• Proto-Oncogene Proteins c-bcl-2
• beauvericin
• Cytochromes c
• CASP3 protein, human
• Caspase 3
• Caspases

Topics

• Antineoplastic Agents (pharmacology)
• Apoptosis
• Carcinoma, Non-Small-Cell Lung
• Caspase 3
• Caspases (metabolism)
• Cell Line, Tumor
• Cell Survival (drug effects)
• Cytochromes c (metabolism)
• DNA Fragmentation
• Depsipeptides (pharmacology)
• Humans
• In Situ Nick-End Labeling
• Lung Neoplasms
• Membrane Potentials (drug effects)
• Mitochondria (drug effects, metabolism, physiology)
• Proto-Oncogene Proteins c-bcl-2 (metabolism)