Antiproliferative activity and apoptosis-inducing mechanism of constituents from Toona sinensis on human cancer cells

BACKGROUND: Natural products, including plants, microorganisms and marines, have been considered as valuable sources for anticancer drug discovery. Many Chinese herbs have been discovered to be potential sources of antitumor drugs. METHODS: In the present study, we investigated the antitumor efficacy of the compounds isolated from Toona sinensis, an important herbal medicine. The inhibitory activities of these compounds were investigated on MGC-803, PC3, A549, MCF-7, and NIH3T3 cells in vitro by MTT assay. The mechanism of the antitumor action of active compounds was investigated through AO/EB staining, Hoechst 33258 staining, TUNEL assay, flow cytometry analysis, and western blotting analysis. RESULTS: Fifteen compounds were isolated from the roots of Toona sinensis. Betulonic acid (BTA) and 3-oxours-12-en-28-oic acid (OEA) isolated from the plant inhibited the proliferation of MGC-803 and PC3 cells, with IC(50) values of 17.7 μM and 13.6 μM, 26.5 μM and 21.9 μM, respectively. Both could lead to cell apoptosis, and apoptosis ratios reached 27.3% and 24.5% in MGC-803 cells at 72 h after treatment at 20 μM, respectively. Moreover, the study of cancer cell apoptotic signaling pathway indicated that both of them could induce cancer cell apoptosis through the mitochondrial pathway, involving the expressions of p53, Bax, caspase 9 and caspase 3. CONCLUSIONS: The study shows that most of the compounds obtained from Toona sinensis could inhibit the growth of human cancer cells. Furthermore, BTA and OEA exhibited potent antitumor activities via induction of cancer cell apoptosis.