{"database":"biostudies-literature","file_versions":[],"scores":null,"additional":{"submitter":["Qian W"],"funding":["NCATS NIH HHS","NCI NIH HHS","NIGMS NIH HHS"],"pagination":["4180-94"],"full_dataset_link":["https://www.ebi.ac.uk/biostudies/studies/S-EPMC4147315"],"repository":["biostudies-literature"],"omics_type":["Unknown"],"volume":["5(12)"],"pubmed_abstract":["Overcoming platinum drug resistance represents a major clinical challenge in cancer treatment. We discovered a novel drug combination using cisplatin and a class of thioquinazolinone derivatives including mdivi-1 (mitochondrial division inhibitor-1), that induces synergistic apoptosis in platinum resistant tumor cells, including those from cisplatin-refractory endstage ovarian cancer patients. However, through study of the combination effect on Drp1 (the reported target of mdivi-1) knockout MEF cells and the functional analysis of mdivi-1 analogs, we revealed that the synergism between mdivi-1 and cisplatin is Drp1-independent. Mdivi-1 impairs DNA replication and its combination with cisplatin induces a synergistic increase of replication stress and DNA damage, causing a preferential upreg"],"journal":["Oncotarget"],"pubmed_title":["Novel combination of mitochondrial division inhibitor 1 (mdivi-1) and platinum agents produces synergistic pro-apoptotic effect in drug resistant tumor cells."],"pmcid":["PMC4147315"],"funding_grant_id":["P50 CA121973","P30 CA047904","P30CA047904","P50 CA097190","P50CA121973","R01 CA169291","P50CA097190","UL1 TR000005","R01 GM096208"],"pubmed_authors":["Qian W","Llambi F","McDermott LA","Roginskaya V","Stolz DB","Edwards RP","Wang J","Van Houten B","Green DR"],"additional_accession":[]},"is_claimable":false,"name":"Novel combination of mitochondrial division inhibitor 1 (mdivi-1) and platinum agents produces synergistic pro-apoptotic effect in drug resistant tumor cells.","description":"Overcoming platinum drug resistance represents a major clinical challenge in cancer treatment. We discovered a novel drug combination using cisplatin and a class of thioquinazolinone derivatives including mdivi-1 (mitochondrial division inhibitor-1), that induces synergistic apoptosis in platinum resistant tumor cells, including those from cisplatin-refractory endstage ovarian cancer patients. However, through study of the combination effect on Drp1 (the reported target of mdivi-1) knockout MEF cells and the functional analysis of mdivi-1 analogs, we revealed that the synergism between mdivi-1 and cisplatin is Drp1-independent. Mdivi-1 impairs DNA replication and its combination with cisplatin induces a synergistic increase of replication stress and DNA damage, causing a preferential upreg","dates":{"release":"2014-01-01T00:00:00Z","publication":"2014 Jun","modification":"2025-04-22T16:52:19.693Z","creation":"2019-03-27T01:34:48Z"},"accession":"S-EPMC4147315","cross_references":{"pubmed":["24952704"],"doi":["10.18632/oncotarget.1944"]}}