Se-methylselenocysteine induces apoptosis through caspase activation and Bax cleavage mediated by calpain in SKOV-3 ovarian cancer cells

Authors
Jun-Kyu YeoSoon-Do ChaChi-Heum ChoSang-Pyo KimJae-We ChoWon-Ki BaekMin-Ho SuhTaeg Kyu KwonJong-Wook ParkSeong-Il Suh
Department
Dept. of Immunology (면역학); Dept. of Microbiology (미생물학); Dept. of Obstetrics & Gynecology (산부인과학); Dept. of Pathology (병리학)
Issue Date
2002
Citation
Cancer Letters, Vol.182(1) : 83-92, 2002
ISSN
0304-3835
Abstract
Se-methylselenocysteine (Se-MSC) is a potent chemopreventive agent in many test systems and has been shown to inhibit tumor promotion and induce apoptosis, but its mechanism of action is still not well understood. The present study was designed to assess the mechanism of Se-MSC on the induction of apoptosis in SKOV-3 ovarian cancer cells. Se-MSC displayed strong inhibitory effects on cell proliferation and viability of SKOV-3 cells in dose and time dependent manners and induced apoptosis. Investigation of the mechanism of Se-MSC-induced apoptosis revealed that treatment with Se-MSC produced morphological features of apoptosis and DNA fragmentation. This was associated with caspase-3 activation and cleavage of poly(ADP-ribose) polymerase and phospholipase C-γ1 proteins. However, SKOV-3 cells treated with Se-MSC did not demonstrate cytochrome c accumulation in the cytosol during apoptosis induction. Pretreatment of cells with the caspase inhibitors (z-VAD-fmk and DEVD-CHO) prevented Se-MSC-induced apoptosis. These results suggested that Se-MSC induces apoptosis through cytochrome c-independent caspase-3 activation in SKOV-3 cells. In late stage of apoptosis, p18 kDa fragment of Bax was generated with the down-regulation of the expressions of survivin, X-linked inhibitor of apoptosis protein, and human inhibitor of apoptosis protein 1 following Se-MSC treatment, suggesting that the modulation of Bax and IAP (inhibitors of apoptosis) family proteins play some role in Se-MSC-mediated apoptosis. Pre-treatments of z-VAD-fmk and the calpain inhibitor, calpeptin inhibited Bax cleavage. These results suggested that Bax cleavage is mediated by calpain, and calpain activation may be a caspase-dependent one. Taken together, the chemopreventive effects of Se-MSC may be related in part to the caspase-3 activation, the down-regulation of IAP family proteins, and Bax cleavage mediated by caspase-dependent calpain activation. Keywords : Se-methylselenocysteine; Caspase; Calpain; Bax
URI
http://kumel.medlib.dsmc.or.kr/handle/2015.oak/35315
Appears in Collections:
1. Journal Papers (연구논문) > 1. School of Medicine (의과대학) > Dept. of Immunology (면역학)
1. Journal Papers (연구논문) > 1. School of Medicine (의과대학) > Dept. of Microbiology (미생물학)
1. Journal Papers (연구논문) > 1. School of Medicine (의과대학) > Dept. of Obstetrics & Gynecology (산부인과학)
1. Journal Papers (연구논문) > 1. School of Medicine (의과대학) > Dept. of Pathology (병리학)
Keimyung Author(s)
백원기; 서민호; 서성일; 차순도; 조치흠; 김상표; 권택규; 박종욱
Full Text
http://lps3.www.sciencedirect.com.proxy.dsmc.or.kr/science/article/pii/S0304383502000757?via%3Dihub
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