Abstract 1709: The effect of a XIAP inhibitor, embelin, on apoptosis of thyroid cancer cell lines

Abstract

Abstract X-linked inhibitor of apoptosis protein (XIAP) is a member of the inhibitor of apoptosis (IAP) protein family that selectively blocks caspases-3, -7, -9 and inhibits cell death. Embelin, a XIAP inhibitor, is known to exhibit anti-inflammatory and apoptotic activities. Recent reports suggest that embelin interferes the signal transducer and activator of transcription 3 (STAT3) pathway and nuclear factor-kB (NF-kB) signal pathway. In this study, we investigated the anti-cancer efficacy of embelin by measuring its effects on apoptosis of thyroid cancer cell lines. We also explored the mechanism underlying these effects. We found that embelin induced the apoptosis of human thyroid cancer cell lines, such as FTC-133, CAL-62, KTC-1, and 8505C. The effect was stronger in BRAF V600E-mutant thyroid cancer cell lines (KTC-1 and 8505C) than wild-type cell lines (FTC-133 and CAL-62). The effect of embelin on cell apoptosis was associated with increased phosphorylation of p38. SB203580 inhibited the embelin mediated induction of cleaved caspase-3 activity in V600E mutant thyroid cancer cell lines. Interestingly, embelin induced apoptosis in BRAF wild type cancer cell lines, even after treatment of SB203580. These results indicated that another signaling pathway, not a p38 pathway, might be existed for embelin induced apoptosis in BRAF wild type thyroid cancer cell. In conclusion, embelin-induced XIAP suppression resulted in an increase of apoptosis via phosphorylation of p38 in BRAF V600E-mutant thyroid cancer cell lines. Regulation of XIAP activity may be potentially useful as a treatment of thyroid cancer, especially in BRAF V600E-mutant thyroid cancer. Citation Format: {Authors}. {Abstract title} [abstract]. In: Proceedings of the 103rd Annual Meeting of the American Association for Cancer Research; 2012 Mar 31-Apr 4; Chicago, IL. Philadelphia (PA): AACR; Cancer Res 2012;72(8 Suppl):Abstract nr 1709. doi:1538-7445.AM2012-1709