Dexamethasone protects against cisplatin-induced activation of the mitochondrial apoptotic pathway in human osteosarcoma cells

Background: Dexamethasone (Dx) is often used to alleviate the acute emetic toxicity associated with high dose cisplatin (cDDP) in osteosarcoma patients. However, in other tumour cell types, Dx has been reported to induce partial resistance to anticancer drugs. Materials and Methods: We examined the effect of Dx on cDDP-induced apoptosis in the HOS human osteosarcoma cell line. Results: Exposure to cDDP, induced apoptosis via the mitochondrial apoptotic pathway as evidenced by cytochrome c release and caspase activation. Pre and cotreatment of HOS cells with Dx reduced cDDP induced apoptosis by 10-25%. Investigation of the mechanisms of this protective effect indicated both the upregulation of the survival factor Akt and a possible direct receptor-mediated action of Dx to attenuate the activation of the mitochondrial apoptotic pathway components. Conclusions: These data indicate the need to carefully address the timing of glucocorticoid use in the clinical management of cancer patients. ©2006 Landes Bioscience.