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.