Abstract B69: Potential cancer chemopreventive compounds from Oplopanax horridus, a native North American plant

Abstract

Abstract Distributed throughout the west of North America, the plant Oplopanax horridus, or devil's club, belongs to the genus Oplopanax, which consists of three species (O. elatus, O. japonicus and O. horridus). Although many studies on the other two species have been performed, phytochemical and pharmacological investigations on O. horridus have been limited, especially cancer chemopreventive studies. After comparing differences of antiproliferative potentials among different plant parts of O. horridus, the root bark was selected to perform further phytochemical isolation to prepare active anticancer fractionations and compounds. The hydrophobic fractions showed potent antiproliferative effects on human HCT-116 and SW-480 colorectal cancer cells. Subsequent isolation of the hydrophobic fractions gave six polyynes and one polyene; in which two novel compounds, Oplopantriol A and Oplopantriol B, were obtained and their absolute structures were elucidated by detailed spectroscopic analyses, including 1D and 2D NMR techniques and chemical methods. The content of these seven compounds in the O. horridus root bark was determined using an on-line SPE-HPLC method. Pharmacological studies showed that two polyynes, including a novel compound (Oplopantriol A), possessed strong cancer cell inhibitory activities (P < 0.001). The IC50 of these two polyynes were observed at 1-5 µM on the colorectal cancer cells. Treatment with active fraction and compounds noticeably induced apoptosis, and distinctly induced the G2/M phase arrest of the cell cycle in a time- and concentration-dependent manner. The trend of increasing cyclin A and cyclin B1 were similar to the increase of G2/M phase cells in all treated groups. These results suggested that active O. horridus fraction and selected polyynes had potential antiproliferative activities on human colorectal cancer cells. The observed cancer chemopreventive effects could be related to the induction of apoptosis and regulation of cell cycle transition. (This work was supported in part by the NIH/NCCAM grants AT003255, AT004418 and AT005362). Citation Information: Cancer Prev Res 2010;3(12 Suppl):B69.