Study of the anti-proliferative activity of 5-substituted 4,7-dimethoxy-1,3-benzodioxole derivatives of sy-1 from Antrodia camphorata on human COLO 205 colon cancer cells

A set of 10 4,7-dimethoxy-1,3-benzodioxole derivatives based on a lead compound previously discovered by our group, SY-1, which was isolated from Antrodia camphorata, were evaluated for their in vitro inhibitory activity on human colorectal carcinoma cells (COLO 205). Structure-activity relationship studies of the 10 compounds indicated the importance of the chain length of the alkyl group at the 5-position, and the 2-propenyl substituent named apiole exhibited the most potent inhibitory activity. In the present study, we demonstrate that the SY-1 analogue apiole decreased the proliferation of COLO 205 cells, but not that of normal human colonic epithelial cells (FHC). The G0/G1 cell cycle arrest induced by apiole (75-225μM) was associated with significantly increased levels of p53, p21 and p27 and decreased levels of cyclin D1. Concerning COLO 205 cell apoptosis, apiole (>150M) treatment significantly increased the levels of cleaved caspases 3, 8, 9 and bax/bcl-2 ratio and induced ladder formation in DNA fragmentation assay and sub-G1 peak in flow cytometry analysis. These findings suggest that apiole can suppress COLO 205 cell growth; however, the detailed mechanisms of these processes require further investigation.