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.


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.
Meyer
Stefan
S
Teenage Cancer Trust, Young Oncology Unit, Christie Hospital NHS Trust, Manchester, UK.
Eden
Tim
T
Kalirai
Helen
H
D000932:Antiemetics / Q000627:therapeutic use*; D000970:Antineoplastic Agents / Q000494:pharmacology*; D017209:Apoptosis / Q000187:drug effects*; D015153:Blotting, Western; D001859:Bone Neoplasms / Q000188:drug therapy* / Q000378:metabolism / Q000473:pathology; D061945:Caspase Inhibitors; D020169:Caspases / Q000378:metabolism; D002945:Cisplatin / Q000494:pharmacology*; D045304:Cytochromes c / Q000378:metabolism; D003907:Dexamethasone / Q000627:therapeutic use*; D004789:Enzyme Activation / Q000187:drug effects; D006801:Humans; D007124:Immunoenzyme Techniques; D008928:Mitochondria / Q000187:drug effects* / Q000378:metabolism; D012516:Osteosarcoma / Q000188:drug therapy* / Q000378:metabolism / Q000473:pathology; D051057:Proto-Oncogene Proteins c-akt / Q000378:metabolism; D011965:Receptors, Glucocorticoid / Q000378:metabolism; D014407:Tumor Cells, Cultured
D000932:Antiemetics; D000970:Antineoplastic Agents; D061945:Caspase Inhibitors; D011965:Receptors, Glucocorticoid; D003907:Dexamethasone; D045304:Cytochromes c; D051057:Proto-Oncogene Proteins c-akt; D020169:Caspases; D002945:Cisplatin