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

2.50
Hdl Handle:
http://hdl.handle.net/10541/72586
Title:
Dexamethasone protects against Cisplatin-induced activation of the mitochondrial apoptotic pathway in human osteosarcoma cells.
Authors:
Meyer, Stefan; Eden, Tim O B; Kalirai, Helen
Abstract:
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.
Affiliation:
Teenage Cancer Trust, Young Oncology Unit, Christie Hospital NHS Trust, Manchester, UK.
Citation:
Dexamethasone protects against Cisplatin-induced activation of the mitochondrial apoptotic pathway in human osteosarcoma cells. 2006, 5 (8):915-20 Cancer Biol. Ther.
Journal:
Cancer Biology & Therapy
Issue Date:
Aug-2006
URI:
http://hdl.handle.net/10541/72586
PubMed ID:
16855374
Type:
Article
Language:
en
ISSN:
1538-4047
Appears in Collections:
All Christie Publications

Full metadata record

DC FieldValue Language
dc.contributor.authorMeyer, Stefan-
dc.contributor.authorEden, Tim O B-
dc.contributor.authorKalirai, Helen-
dc.date.accessioned2009-07-06T14:05:18Z-
dc.date.available2009-07-06T14:05:18Z-
dc.date.issued2006-08-
dc.identifier.citationDexamethasone protects against Cisplatin-induced activation of the mitochondrial apoptotic pathway in human osteosarcoma cells. 2006, 5 (8):915-20 Cancer Biol. Ther.en
dc.identifier.issn1538-4047-
dc.identifier.pmid16855374-
dc.identifier.urihttp://hdl.handle.net/10541/72586-
dc.description.abstractBACKGROUND: 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.en
dc.language.isoenen
dc.subjectBone Canceren
dc.subjectTumour Cellsen
dc.subject.meshAntiemetics-
dc.subject.meshAntineoplastic Agents-
dc.subject.meshApoptosis-
dc.subject.meshBlotting, Western-
dc.subject.meshBone Neoplasms-
dc.subject.meshCaspases-
dc.subject.meshCisplatin-
dc.subject.meshCytochromes c-
dc.subject.meshDexamethasone-
dc.subject.meshEnzyme Activation-
dc.subject.meshHumans-
dc.subject.meshImmunoenzyme Techniques-
dc.subject.meshMitochondria-
dc.subject.meshOsteosarcoma-
dc.subject.meshProto-Oncogene Proteins c-akt-
dc.subject.meshReceptors, Glucocorticoid-
dc.subject.meshTumor Cells, Cultured-
dc.titleDexamethasone protects against Cisplatin-induced activation of the mitochondrial apoptotic pathway in human osteosarcoma cells.en
dc.typeArticleen
dc.contributor.departmentTeenage Cancer Trust, Young Oncology Unit, Christie Hospital NHS Trust, Manchester, UK.en
dc.identifier.journalCancer Biology & Therapyen

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