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Cytotoxic triterpenes from Antrodia camphorata and their mode of action in HT-29 human colon cancer cells

2009; Elsevier BV; Volume: 285; Issue: 1 Linguagem: Inglês

10.1016/j.canlet.2009.05.002

1872-7980

Chi‐Tai Yeh, Yerra Koteswara Rao, Chih‐Jung Yao, Chuan-Feng Yeh, Chi-Han Li, Shuang‐En Chuang, John H. T. Luong, Gi‐Ming Lai, Yew‐Min Tzeng,

Phytochemistry and Bioactive Compounds

Five lanostane (2, 3, 4, 6 and 8) and three ergostane-type (1, 5 and 7) triterpenes isolated from the fruiting bodies of Antrodia camphorata were evaluated for their in vitro cytotoxic data against various cancer cell types. The three zhankuic acids, 1, 5 and 7 displayed the most potent cytotoxic effect with an IC50 value of 22.3–75.0 μM. The compound 3 was selectively cytotoxic in three colon cancer cell lines (HT-29, HCT-116 and SW-480) and a breast cancer model (MDA-MB-231), whereas 8 only showed its cytotoxicity against MDA-MB-231. None of these isolates was toxic to mammary epithelial (MCF10A) and primary foreskin fibroblast (HS68) cells, two human normal cell lines. The compounds 1, 5 and 7 were also demonstrated to induce apoptosis in HT-29 and SW-480 cells, as confirmed by sub-G1 cell cycle arrest. In HT-29 cells, the expression of apoptosis-associated proteins poly-(ADP-ribose) polymerase cleavage, Bcl-2 and procaspase-3 were suppressed by compounds 1, 5 and 7. A mixture containing 4 μM each of compounds 1, 5 and 7 also showed a synergistic cytotoxic effect in HT-29 cells.