Activation of caspase-8 is critical for sensitivity to cytotoxic anti-Fas anti body-induced apoptosis in human ovarian cancer cells

被引:18
作者
Hayakawa, A
Wu, J
Kawamoto, Y
Zhou, YW
Tanuma, S
Nakashima, I
Suzuki, H
机构
[1] Nagoya Univ, Grad Sch Med, Dept Immunol, Showa Ku, Nagoya, Aichi 4668550, Japan
[2] Nagoya Univ, Grad Sch Med, Dept Equipment Ctr Res & Educ, Showa Ku, Nagoya, Aichi 4668550, Japan
[3] Sci Univ Tokyo, Fac Pharmaceut Sci, Dept Biochem, Shinjuku Ku, Tokyo 1620826, Japan
关键词
apoptosis; caspase-8; DISC; Fas; ovarian cancer cells;
D O I
10.1023/A:1014302212321
中图分类号
Q5 [生物化学]; Q7 [分子生物学];
学科分类号
071010 ; 081704 ;
摘要
Two ovarian cancer cell lines named NOS4 and SKOV-3 have been shown to have different sensitivities to a cytotoxic anti-Fas antibody, CH-11. Although both cell lines express Fas molecules on the cell surfaces at the same intensities, apoptosis is induced by CH-11 in NOS4 cells but not in SKOV-3 cells. In this study, the different apoptosis-sensitivities of these cells were assessed. Both cell lines express almost the same levels of FADD, RIP, c-FLIP, FAP-11, Bax, Bcl-2 and Bcl-XL. Evidence of caspase-8, caspase-9 and caspase-3 activation and of cleavage of PARP and Bid was obtained in NOS4 cells but not in SKOV-3 cells. When triggered by FasL protein, DNA fragmentation and caspase-8 activation were observed in SKOV-3 cells, though they were not as clear as in NOS4 cells. All the anti-Fas antibody-mediated signals for apoptosis induction in NOS4 cells were completely blocked by a caspase-8-specific inhibitor, Z-IETD-FMK. These results indicate that the different sensitivities to the anti-Fas antibody are solely dependent on the activation of caspase-8, which could be influenced by yet unknown qualitative or quantitative abnormalities in molecules involved in DISC formation.
引用
收藏
页码:107 / 113
页数:7
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