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dc.contributor.authorChalita Kingnateen_US
dc.contributor.authorKittipat Charoenkwanen_US
dc.contributor.authorSirinart Kumfuen_US
dc.contributor.authorNattayaporn Apaijaien_US
dc.contributor.authorThidarat Jaiwongkamen_US
dc.contributor.authorSurapan Khunamornpongen_US
dc.contributor.authorNipon Chattipakornen_US
dc.contributor.authorSiriporn C. Chattipakornen_US
dc.description.abstractThe standard chemotherapy regimens of ovarian cancer are platinum-based chemotherapy (carboplatin and paclitaxel) and bevacizumab (BEV). However, the effects of BEV alone or combined with carboplatin and paclitaxel on mitochondrial dynamics, mitochondrial function, mitophagy, apoptosis, inflammation and vascular endothelial growth factor (VEGF) in human ovarian cancer mitochondria and cells have not yet been investigated. Therefore, we aimed to test the hypothesis that 1) platinum-based chemotherapy and BEV equally damage isolated mitochondria from human ovarian cancers, and ovarian cancer cells through inducing mitochondrial dynamics dysregulation, mitochondrial dysfunction, increased mitophagy and apoptosis, as well as altered inflammation and VEGF; and 2) combined therapies exert greater damage than monotherapy. Each isolated human ovarian cancer mitochondria (n = 16) or CaOV3 cells (n = 6) were treated with either platinum-based chemotherapy (carboplatin 10 μM and paclitaxel 5 μM), BEV (2 mg/mL) or combined platinum-based chemotherapy and BEV for 60 min or 24 h, respectively. Following the treatment, mitochondrial dynamics, mitochondrial function, mitophagy, apoptosis, cytotoxicity, inflammation and VEGF were determined. Platinum-based chemotherapy caused ovarian cancer mitochondria and cell damage through mitochondrial dysfunction, increased cell death with impairment of membrane integrity, and enhanced VEGF reduction, while BEV did not. BEV caused deterioration of ovarian cancer mitochondria and cells through mitochondrial-dependent apoptosis, but it had no effect on cell viability. Interestingly, combined platinum-based chemotherapy and BEV treatments had no addictive effects on all parameters except mitochondrial maximal respiration, when compared to monotherapy. Collectively, these findings suggest that platinum-based chemotherapy and BEV caused human ovarian cancer mitochondrial and cell damage through different mechanisms.en_US
dc.subjectBiochemistry, Genetics and Molecular Biologyen_US
dc.subjectPharmacology, Toxicology and Pharmaceuticsen_US
dc.titlePlatinum-based chemotherapy and bevacizumab instigate the destruction of human ovarian cancers via different signaling pathwaysen_US
article.title.sourcetitleBiochemical Pharmacologyen_US
article.volume188en_US Hospitalen_US Mai Universityen_US
Appears in Collections:CMUL: Journal Articles

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