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Life Sci. 2006 Jan 2;78(6):607-13. Epub 2005 Aug 19.

Dehydrotrametenolic acid selectively inhibits the growth of H-ras transformed rat2 cells and induces apoptosis through caspase-3 pathway.

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1
Korea Research Institute of Bioscience and Biotechnology, 52 Uendong, Yusung, Taejon, Republic of Korea.

Abstract

The screening of natural products that preferentially inhibit growth of H-ras transformed rat2 cells vs. rat2 cells was performed to identify H-ras specific growth inhibitor. A lanostane-type triterpene acid, dehydrotrametenolic acid (3beta-hydroxylanosta-7,9(11),24-trien-21-oic acid), was isolated from the sclerotium of Poria cocos (Polyporaceae). Dehydrotrametenolic acid selectively inhibited the growth of H-ras transformed cells with a GI(50) value of 40 microM. FACS analysis indicated that the compound exerted its anti-proliferation effects through cell cycle arrest at G2/M phase and accumulation of sub-G1 population. Dehydrotrametenolic acid-induced apoptosis was further confirmed with chromosomal DNA fragmentation, caspase-3 activation, and degradation of PARP and Lamin A/C degradation. The compound also regulated the expression of H-ras, Akt and Erk, which are the downstream proteins of H-ras signaling pathways. The results suggest that dehydrotrametenolic acid can be a potential anticancer agent against H-ras transformed tumor.

PMID:
16112686
DOI:
10.1016/j.lfs.2005.05.066
[Indexed for MEDLINE]

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