Diosgenin-3- O -alpha- l -rhamnopyranosyl-(1-->4)-beta- d -glucopyranoside (DRG) is a well-known pentacyclic triterpene glycoside newly isolated from the rhizomes of Dioscorea futschauensis R. Kunth (Dioscoreaceae) by our group. In the present work, the inhibitory effect of DRG on the cell proliferation of human cancer cell lines was examined to reveal for the first time that DRG shows stronger anticancer activity than that of the positive control cisplatin. DRG inhibited the proliferation of human cancer cells, A431, A2780, A549, K562, and HCT-15, with IC 50 (mumol L -1 ) values of 9.33+/-0.22, 18.7+/-0.16, 9.98+/-0.38, 6.44+/-0.10, and 5.86+/-0.14 respectively. It was then found, by morphological observation, "DNA ladder" detection and flow cytometric analysis, that DRG exerts its anticancer effect through inducing apoptosis on HCT-15 cells. Furthermore, it has been demonstrated that DRG triggers a mitochondria-controlled apoptotic pathway to induce apoptosis on HCT-15 cells, which involves the reduction of the mitochondrial potential (Delta psi m ), the release of cytochrome c from mitochondria into the cytosol, and the down-regulation of the ratio of Bcl-2/Bax expression level. The present results reasonably suggest that regulating the balance of Bcl-2/Bax expression level plays a key role in the DRG-induced apoptosis. Such findings provide novel knowledge to elucidate the biological properties of DRG, even though DRG was discovered early in the late 1960s. These results suggest that DRG may be a good candidate as a chemotherapeutic agent to treat human colon carcinoma.
