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Diosgenin-3-O-α-l-Rhamnopyranosyl-(1→4)-β-d-glucopyranoside obtained as a new anticancer agent from Dioscorea futschauensis induces apoptosis on human colon carcinoma HCT-15 cells via mitochondria-controlled apoptotic pathway

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Diosgenin-3-O-α-l-rhamnopyranosyl-(1→4)-β-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
(μmol 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 (Δψ
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.
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Keywords: Apoptosis; Bax; Bcl-2; Cytochrome; Diosgenin-3--α--rhamnopyranosyl-(1→4)---glucopyranoside; HCT-15 cells; Mitochondrial transmembrane potential

Document Type: Research Article

Affiliations: 1: The School of Traditional Chinese Materia Medica Shenyang Pharmaceutical University 110016 Shenyang China 2: Tianjin Institute for Biomedicinal Research (TIBiR) 3rd Floor of D2-Building Xinmao Technology Park Huayuan Industrial District 300384 Tianjin China 3: Marine Drug and Food Insitute Ocean University of China 266003 Qingdao China 4: Traditional Chinese Medicines & Natural Products Research Center Shenzhen 518057 Shenzhen China

Publication date: June 1, 2004

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