A novel steroid and cytotoxic constituents from Dioscorea membranacea Pierre against hepatocellular carcinoma and cholangiocarcinoma cells.

ETHNOPHARMACOLOGICAL RELEVANCE: The rhizomes of Dioscorea membrancea Pierre have been used in Thai traditional medicine as an ingredient formula for liver cancer and cholangiocarcinoma treatment.

AIM OF THE STUDY: To investigate the cytotoxic activity of ethanolic extract and constituents of D. membrancea to support its traditional use.

MATERIALS AND

METHODS

The SRB assay was used to determine the cytotoxic activity against hepatocellular carcinoma (HepG2), cholangiocarcinoma (KKU-M156) cells and one normal human keratinocyte immortal cells (HaCaT) with its ethanolic extract and isolated compounds. Bioassay guided isolation was used for isolating cytotoxic compounds.

RESULTS

The ethanolic extract of D. membranacea rhizome showed weak cytotoxic against KKU-M156 and HepG2 (IC50 at 72h exposure=30.49±0.82 and 38.97±2.04µg/mL respectively). A new steroid [epipanthogenin B (1)], a known steroid [panthogenin B (2)], two napthofuranoxepins [dioscorealide A (3) and dioscorealide B (4)], phenanthraquinone [dioscoreanone (5)] and two phenanthrene [5,6-dihydroxy-2,4-dimethoxy-9,10-dihydrophenanthrene (6) and 2,5,6-trihydroxy-3,4-dimethoxy, 9, 10-dihydrophenanthrene (7)] were isolated from active chloroform fraction. Compound 4 showed the highest cytotoxicity against HepG2 (IC50 at 72h exposure=2.87±0.21µM) and KKU-M156 (IC50 at 72h exposure=1.67±0.10µM) and less toxicity against normal cell line (HaCaT) (IC50 at 72h exposure>100µM). Compound 5 showed selective cytotoxic activity against KKU-M156 (IC50 at 72h exposure=3.46±0.11µM). Compounds 6 and 7 showed weak cytotoxic activity against HepG2 (IC50 at 72h exposure=24.96±2.32 and 51.31±3.52µM). Compounds (1-3) showed no cytotoxic activity against HepG2 and KKU-M156 cell lines (IC50 at 72 h exposure>100µM).

CONCLUSION

Seven compounds were isolated from active chloroform fraction of the ethanolic extract of D. membranacea rhizomes. Only dioscorealide B (4) might be served as a good anticancer agent for liver cancer and cholangiocarcinoma cancer because it can kill cancer cell but not toxic on normal cell. This research support Thai traditional medicine use of D. membranacea for liver cancer and cholangiocarcinoma cancer treatment.