Effects of triterpene derivatives from Maytenus rigida on VEGF-induced Kaposi's sarcoma cell proliferation

Betulinic acid (BA) is a naturally occurring lupane-type triterpene which exhibits a variety of biological activities including potent cytotoxic properties. On the basis of the structural similarity to BA, two lupane derivatives namely lup-20(29)-ene-3beta,30-diol (1) and lup-20(29)-ene-3beta,28-diol (2), along with two friedelane derivatives, namely friedelan-3-one (3) and friedelan-3beta-ol (4), isolated from the Brazilian plant Maytenus rigida, have been evaluated for their anti-proliferative effect. Similarly to BA, compounds 1 and 3 at 1 microM concentration significantly inhibited the VEGF-induced Kaposi's sarcoma (KS) cell proliferation by 50%. In contrast, this effect was not found in control endothelial cells (EC). Moreover, compounds 1 and 3 showed a dose-dependent effect on the apoptotic cell death, as detected by FACS analysis and caspase-3 assay. Specifically, at 10 microM concentration, apoptosis was significantly induced (from 45% to 55% of hypodiploid cells vs control cells) and showed the same potency order observed for the anti-proliferative effect at 1 microM, i.e., compound 3>BA>compound 1. Taking into account the interest given rise by BA as anticancer agent, the comparable anti-proliferative activity shown by compounds 1 and 3 and BA, can give an impulse to further investigate lupane and friedelane derivatives as cytotoxic agents.