Abstract 780: Dimethyl cardamonin induces G1-phase cell cycle arrest, apoptosis, and autophagy in HCT116 cells

Abstract

Abstract Dimethyl cardamonin (2’,4’-dihydroxy-6’-methoxy-3’,5’-dimethylchalcone; DMC) is a naturally occurring chalcone, and it is the major compound isolated from the leaves and/or fruits of Syzygium samarangense (Blume) Merr. & L.M. Perry (Myrtaceae). DMC has been reported to have anti-diabetic, anti-bacterial, spasmolitic and anti-tumor properties. Furthermore, it has been used as an antipyretic and a diuretic agent in Taiwan folk medicine. However, the underlying mechanisms of its anti-tumor effects have not been studied. Here, we report that DMC induced G1 phase arrest, apoptosis and autophagy in HCT116 cell line. In this study, DMC decreased the expression of the phospho-Rb, CDK4 and cyclin D1 expression level, which is correlated with G1 phase. We also found that DMC-induced apoptosis occurred through the p53 dependent manner and the mitochondrial death pathway as evidenced by reduction of the Bcl2, XIAP and caspase-9 activation, and by induction of Bims. And, we showed that DMC up-regulates activity of JNK and p38. Interestingly, we found that DMC elicits autophagy, a process that participates in apoptotic response, in a JNK and p53-dependent manner, in HCT116 cell line. We also found that the increased activation of JNK by DMC is partially regulated by p53, highlighting the relationship of JNK and autophagy to p53 signaling pathway. The treatment of HCT116 (p53 -/-) cell line with DMC resulted in reduction in both apoptotic and autophagic effects relative to HCT116 (p53 +/+) cell line. This study suggested that DMC induced the multiple effects of G1 phase arrest, apoptosis and autophagy through JNK and p53 in HCT 116 cell line. Citation Format: {Authors}. {Abstract title} [abstract]. In: Proceedings of the 101st Annual Meeting of the American Association for Cancer Research; 2010 Apr 17-21; Washington, DC. Philadelphia (PA): AACR; Cancer Res 2010;70(8 Suppl):Abstract nr 780.