Cytotoxic triterpenes from Antrodia camphorata and their mode of action in HT-29 human colon cancer cells.
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 IC(50) value of 22.3-75.0microM. 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 4microM each of compounds 1, 5 and 7 also showed a synergistic cytotoxic effect in HT-29 cells.
Yeh
Chi-Tai
CT
National Institute of Cancer Research, Zhunan, Taiwan, ROC.
Rao
Yerra Koteswara
YK
Yao
Chih-Jung
CJ
Yeh
Chuan-Feng
CF
Li
Chi-Han
CH
Chuang
Shuang-En
SE
Luong
John H T
JH
Lai
Gi-Ming
GM
Tzeng
Yew-Min
YM
D000970:Antineoplastic Agents / Q000302:isolation & purification / Q000494:pharmacology*; D055491:Antrodia / Q000737:chemistry*; D017209:Apoptosis / Q000187:drug effects; D053148:Caspase 3 / Q000378:metabolism; D002453:Cell Cycle / Q000187:drug effects; D049109:Cell Proliferation / Q000187:drug effects; D002470:Cell Survival / Q000187:drug effects; D003110:Colonic Neoplasms / Q000378:metabolism / Q000473:pathology*; D004305:Dose-Response Relationship, Drug; D004357:Drug Synergism; D004789:Enzyme Activation; D048690:Fruiting Bodies, Fungal / Q000737:chemistry; D019073:HT29 Cells; D006801:Humans; D020128:Inhibitory Concentration 50; D011065:Poly(ADP-ribose) Polymerases / Q000378:metabolism; D019253:Proto-Oncogene Proteins c-bcl-2 / Q000378:metabolism; D014315:Triterpenes / Q000302:isolation & purification / Q000494:pharmacology*
D000970:Antineoplastic Agents; D019253:Proto-Oncogene Proteins c-bcl-2; D014315:Triterpenes; D011065:Poly(ADP-ribose) Polymerases; C505407:CASP3 protein, human; D053148:Caspase 3