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

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.