Abstract 4963: Tanshinone IIA induces JNK-dependent intrinsic apoptosis via suppressing astrocyte-elevated gene 1 expression in chronic myelogenous leukemia KBM-5 cells

Abstract

Abstract Tanshinone IIA (Tan IIA) is a phytochemical isolated from the root of Salviae miltiorrhizae (Danshen) and has been reported to have various biological activities such as anti-inflammation, anti-oxidation and anti-cancer. However, the underlying molecular mechanisms to control anti-cancer effect of Tan IIA in chronic myelogenous leukemia (CML) have not been fully understood yet. In the present study, we investigated whether Tan IIA has the anti-cancer potential by inducing apoptosis in CML cells. Tan IIA significantly decreased the viability of human CML KBM-5 cells, but not normal peripheral blood lymphocytes. Tan IIA induced apoptotic cell death by increasing the sub-G1 cell populations and stimulating atypical shrunken of nucleus and DNA fragmentation. Also, Tan IIA significantly reduced the mitochondrial membrane potential, stimulated the release of cytochrome C from mitochondria into the cytosol and activated intrinsic caspase cascade. Furthermore, Tan IIA enhanced phosphorylation of JNK and suppressed the expression of astrocyte-elevated gene-1 (AEG-1). In contrast, blocking JNK activity using JNK inhibitor SP600125 reversed Tan IIA-induced apoptosis and AEG-1 expression. Taken together, our findings suggest that Tan IIA induces JNK-dependent intrinsic apoptosis via suppressing AEG-1 expression in KBM-5 cells as a valuable candidate agent for CML therapy. 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 4963. doi:1538-7445.AM2012-4963