Despite developing refinements of chemotherapy regimens for osteosarcoma, multi-drug resistant cases are frequently seen and patients with metastatic or recurrent disease continue to have a very poor prognosis. Recently, the expression of the longevity gene Sirt1 was found to be relatively higher expressed in tumors compared with the normal tissues. Association of high level of Sirt1 expression with the development of multi-drug resistance in tumor cells has also been indicated. Thus, it is interesting to study the therapeutic potential of regulating Sirt1 activity for the treatment of osteosarcoma.

In the present study, we evaluated the effects of two Sirt1 activators, resveratrol and isonicotinamide, on growth and apoptosis in four human osteosarcoma cell lines, HOS, Saos-2, U-2 OS and MG-63. We found that Sirt1 protein was expressed in all osteosarcoma cell lines. Instead of promoting cell survival, both resveratrol and isonicotinamide decreased cell growth and induced cell apoptosis in a dose-dependent fashion. Furthermore, the pro-apoptotic effect of resveratrol could be enhanced by L-asparaginase-induced nutrition restriction of cultured osteosarcoma cells.

Our results demonstrated that Sirt1 activators elicited pro-apoptotic effects in osteosarcomas. Thus, Sirt1 could be a potential target in the treatment of osteosarcoma. However, due to the non-specificity of the Sirt1 activators used further studies, such as knock-down of Sirt1 by siRNA, are needed to confirm the effect of Sirt1 activation on malignant cells.