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  • 08월 28일 16시 이후 : 초록수정 불가능, 일정확인 및 검색만 가능

Screening and identification of TRAIL-induced apoptosis modulator : TM 1

2008년 8월 9일 17시 39분 20초
33P176포 이곳을 클릭하시면 발표코드에 대한 설명을 보실 수 있습니다.
목 <발표Ⅰ>
저자 및
황미경, 민용기, 김성환
한국화학연구원 신약기반기술센터 화학유전체 연구실, Korea
Tumor necrosis factor-related apoptosis-inducing ligand (TRAIL) preferentially triggers apoptosis in tumor cells versus normal cells, thus providing a therapeutic potential. Many studies have shown that the apoptosis-inducing activity of TRAIL can be enhanced by various cancer therapeutic agents. In this study, we investigated the effects of TRAIL-induced apoptosis modulator, TM1 on the growth of human lung cancer cells and the induction of apoptosis; TM1 induced apoptosis in TRAIL – resistant human lung cancer cell line H1299 and exhibited an augmented effect on the induction of apoptosis when combined with recombinant TRAIL. Blockage of TM1-binding partner expression by small interfering RNA (siRNA) also showed to enhance TRAIL-induced apoptosis, indicating that TM1 augmented TRAIL-induced apoptosis. Moreover, we found that TM1 down-regulated the expression of Bcl-XL , a repressor of apoptosis, cIAPs and XIAP, the key members of intrinsic inhibitors of apoptosis (IAP) protein. We also demonstrated that direct interaction between TM1-binding partner and c-FLIPL, but not FADD or caspase 8, and that TM1 inhibited the TM1-binding partner–FLIP binding concurrent with inhibition of ERK phosphorylation, a downstream signal of FLIP. We analyzed TRAIL-induced DISC in TRAIL-resistant human lung cancer cell line and showed that TM1 inhibited that c-FLIPL was recruited to the TRAIL-mediated DISC. These results suggested that TM1 might be involved in the TRAIL-induced apoptosis signaling pathway and formation of TRAIL-mediated death DISC. Thus, our findings showed the efficacy of TM1 in human lung cancer cells suggesting that TM1 may be used in combination with TRAIL for treatment of human lung cancer