Abstract 4229: Dichamanetin, a C-benzylated flavonoid from Piper sarmentosum inhibits cell growth and induces G1 cell cycle arrest in cancer cells through mitochondrial-mediated apoptosis

Dichamanetin (C29H24O6) is a rare C-benzylated flavanoid isolated as a major metabolite from Piper sarmentosum Roxb. (Piperaceae). Dichamanetin significantly decreased the cell viability of various types of cancer cells in a dose- and time-dependent manner, characterized by G1 arrest of the cell cycle. In the present study, we investigated the molecular mechanism whereby dichamanetin exerts its cytotoxic effect on human cancer cells in vitro. We examined the involvement of ROS-signaling components (ROS levels, NF-kB transcription factor, mitochondrial membrane potential, DNA damage, and proteasome inhibition) and demonstrated that the antiproliferative effect of cancer cells is partially mediated by induction of oxidative stress. Dichamanetin treatment did not significantly inhibited proteasome, but inhibited moderately PARP-1 enzyme activity. Additionally, FACS analysis with JC-1 fluorescent dye established significant deviation of mitochondrial membrane potential by dichamanetin in treated cells. The present data therefore supports dichamanetin as an active anti-proliferative metabolite that acts in part through mitochondrial-mediated apoptosis. Acknowledgment This research was supported by Program Project Grant P01-CA125066 funded by the National Cancer Institute, NIH. We also wish to acknowledge the plant taxonomists who collected the plant material used in this investigation. Citation Format: {Authors}. {Abstract title} [abstract]. In: Proceedings of the 102nd Annual Meeting of the American Association for Cancer Research; 2011 Apr 2-6; Orlando, FL. Philadelphia (PA): AACR; Cancer Res 2011;71(8 Suppl):Abstract nr 4229. doi:10.1158/1538-7445.AM2011-4229