title: Resveratrol inhibits proliferation and promotes apoptosis of osteosarcoma cells.
abstract: 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.
authors.affiliation: Department for Clinical Science, Intervention and Technology (CLINTEC), Division of Orthopedics, Karolinska Institutet, Huddinge, 14186 Huddinge, Sweden. Yan.Li@ki.se
authors.forename: Yan
authors.initials: Y
authors.lastname: Li
authors.forename: Carl-Magnus
authors.initials: CM
authors.lastname: Bäckesjö
authors.forename: Lars-Arne
authors.initials: LA
authors.lastname: Haldosén
authors.forename: Urban
authors.initials: U
authors.lastname: Lindgren
mesh_terms: D016588:Anticarcinogenic Agents / Q000494:pharmacology*; D017209:Apoptosis / Q000187:drug effects*; D045744:Cell Line, Tumor; D049109:Cell Proliferation / Q000187:drug effects*; D004305:Dose-Response Relationship, Drug; D006131:Growth Inhibitors / Q000494:pharmacology; D006801:Humans; D009536:Niacinamide / Q000378:metabolism; D012516:Osteosarcoma / Q000188:drug therapy*; D000077185:Resveratrol; D056564:Sirtuin 1; D037761:Sirtuins / Q000378:metabolism; D013267:Stilbenes / Q000494:pharmacology*
chemical_list: D016588:Anticarcinogenic Agents; D006131:Growth Inhibitors; D013267:Stilbenes; D009536:Niacinamide; C027681:isonicotinamide; C447939:SIRT1 protein, human; D056564:Sirtuin 1; D037761:Sirtuins; D000077185:Resveratrol