Diosgenin-3-O-alpha-L-rhamnopyranosyl-(1 --> 4)-beta-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.
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 IC50 (micromol 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 (deltapsim), 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.
Tianjin Institute for Biomedicinal Research, 3rd Floor of D2-Building, Xinmao Technology Park, Huayuan Industrial District, Tianjin 300384, China.
San-Long
SL
Wang
Bing
B
Cai
Cheng-Bin
CB
Cui
Hong-Wei
HW
Liu
Chun-Fu
CF
Wu
Xin-Sheng
XS
Yao
D000972:Antineoplastic Agents, Phytogenic / Q000494:pharmacology*; D045744:Cell Line, Tumor; D003110:Colonic Neoplasms / Q000201:enzymology / Q000378:metabolism / Q000473:pathology*; D045304:Cytochromes c / Q000378:metabolism; D027742:Dioscorea / Q000737:chemistry*; D004144:Diosgenin / Q000031:analogs & derivatives / Q000302:isolation & purification* / Q000494:pharmacology; D015536:Down-Regulation; D005434:Flow Cytometry; D006801:Humans; D008564:Membrane Potentials; D008928:Mitochondria / Q000201:enzymology / Q000502:physiology*; D011518:Proto-Oncogene Proteins / Q000378:metabolism; D019253:Proto-Oncogene Proteins c-bcl-2 / Q000378:metabolism; D012503:Saponins / Q000302:isolation & purification* / Q000494:pharmacology; D051028:bcl-2-Associated X Protein
D000972:Antineoplastic Agents, Phytogenic; C494826:BAX protein, human; D011518:Proto-Oncogene Proteins; D019253:Proto-Oncogene Proteins c-bcl-2; D012503:Saponins; D051028:bcl-2-Associated X Protein; C484702:diosgenin-3-O-rhamnopyranosyl-1-4-glucopyranoside; D045304:Cytochromes c; D004144:Diosgenin