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

Abstract

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.

• Authors: 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
• Journal: Cancer letters (Cancer Lett) Vol. 285 Issue 1 Pg. 73-9 (Nov 18 2009) ISSN: 1872-7980 [Electronic] Ireland
• PMID: 19477064 (Publication Type: Journal Article, Research Support, Non-U.S. Gov't)

Chemical References

• Antineoplastic Agents
• Proto-Oncogene Proteins c-bcl-2
• Triterpenes
• Poly(ADP-ribose) Polymerases
• CASP3 protein, human
• Caspase 3

Topics

• Antineoplastic Agents (isolation & purification, pharmacology)
• Antrodia (chemistry)
• Apoptosis (drug effects)
• Caspase 3 (metabolism)
• Cell Cycle (drug effects)
• Cell Proliferation (drug effects)
• Cell Survival (drug effects)
• Colonic Neoplasms (metabolism, pathology)
• Dose-Response Relationship, Drug
• Drug Synergism
• Enzyme Activation
• Fruiting Bodies, Fungal (chemistry)
• HT29 Cells
• Humans
• Inhibitory Concentration 50
• Poly(ADP-ribose) Polymerases (metabolism)
• Proto-Oncogene Proteins c-bcl-2 (metabolism)
• Triterpenes (isolation & purification, pharmacology)