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 (75–225 μM) was associated with significantly increased levels of p53, p21 and p27 and decreased levels of cyclin D1. Concerning COLO 205 cell apoptosis, apiole (>150 μM) 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.