Alpha-tocopheryl succinate alters cell cycle distribution sensitising human osteosarcoma cells to methotrexate-induced apoptosis.

alpha-Tocopheryl succinate (alpha-TOS) exerts pleiotrophic responses in malignant cells leading to cell cycle arrest, differentiation and apoptosis. We tested the ability of alpha-TOS to induce apoptosis or cell cycle perturbation in three human osteosarcoma (OS) cell lines which differ in their pRB and p53 status. We found high levels of apoptosis in OS cells carrying wild-type p53 gene when exposed to alpha-TOS, while the mutant p53 cells were resistant. A S/G2 transition arrest was observed in two OS cell lines exposed to alpha-TOS, which sensitised them to methotrexate, an agent whose activity is cell cycle-dependent. We propose that alpha-TOS may be used as a drug or an adjuvant for treatment of osteosarcomas.