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Lin HI, Lee YJ, Chen BF, Tsai MC, Lu JL, Chou CJ, Jow GM.
Cancer Lett. 2005 Dec 18;230(2):248-59.
Involvement of Bcl-2 family, cytochrome c and caspase 3 in induction of
apoptosis by beauvericin in human non-small cell lung cancer cells.
School of Medicine, Fu Jen Catholic University, 510, Chung-Cheng Road, Hsin-Chuang,
Taipei Hsien 242, Taiwan.
Beauvericin, a cyclic hexadepsipeptide from Codyceps cicadae, possesses
anti-convulsion, anti-arrhythmia, sedation, and anti-tumor activities. It has
been reported that Beauvericin induces apoptosis in several cancer cell lines.
However, the molecular mechanism underlying the Beauvericin -induced apoptotic
process is not yet clearly understood. In the present study, the intracellular
signaling pathways of Beauvericin -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, Beauvericin -induced apoptosis in human NSCLC A549
cells demonstrated a Beauvericin concentration- and treatment time-dependent
manner. This Beauvericin -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
Beauvericin 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 Beauvericin-induced caspase 3 activity
and cell death. These results clearly demonstrate that the induction of
apoptosis by Beauvericin 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 Beauvericin-induced apoptotic process in human NSCLC A549 cells.
PMID: 16297711
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