Resveratrol inhibits proliferation and promotes apoptosis of osteosarcoma cells.

The phytoalexin resveratrol has been described to have chemopreventive and chemotherapeutic effects in several tumor models while its effects on osteosarcoma have not been extensively studied. Additionally, resveratrol is a potent activator of the Sirt1/Sir2 (silent information regulator 2) family of NAD-dependent deacetylases which plays a role in calorie restriction-mediated tumor suppression. In the present study, we evaluated the effect of resveratrol on growth and apoptosis in four osteosarcoma cell lines (HOS, Saos-2, U-2 OS and MG-63) and a normal human osteoblast cell line (NHOst). We found that Sirt1 protein was relatively higher expressed in the tumor cells than normal osteoblasts. Consistently, resveratrol induced apoptosis in a dose-dependent fashion in the osteosarcoma cells but had minor effect on normal osteoblasts. Also, a similar effect could be elicited by another Sirt1 activator, isonicotinamide. In addition, the pro-apoptotic effect of resveratrol could be enhanced by nutrition restriction elicited by l-asparaginase. We postulate that these effects by resveratrol are mediated via Sirt1 but further studies are needed to confirm or refute this theory.