title: Effect of apoptosis-inducing antitumor agents on endocardial endothelial cells.
abstract: Chemotherapy is one of the common treatment modalities for cancer. Some of the antineoplastic drugs have, however, been found to be toxic for vascular endothelium, resulting in complications such as endothelial dysfunction, thromboembolism, heart failure, and cardiomyopathy. In this study, we investigated the cytotoxic effect of widely used antitumor agents doxorubicin, camptothecin, and thapsigargin on primary and immortalized porcine endocardial endothelial cells and compared with the effects of these agents on human umbilical vein endothelial cells, human aortic endothelial cells, and EA.hy926 cells. Our study revealed that endocardial endothelial cells are relatively resistant to apoptosis induced by these drugs. Interestingly, our study indicates that response to antitumor agents greatly differs depending on the site of origin of endothelial cells. Doxorubicin, camptothecin, and thapsigargin induce mitochondrial-dependent cell death following loss of mitochondrial membrane potential (MMP) in vascular endothelial cells, with subsequent increase in sub-G0 population. In endocardial endothelial cells, there was no MMP loss; and only cell cycle arrest either at G1 or S phases was observed when the cells were treated with doxorubicin, camptothecin, and thapsigargin.
authors.affiliation: Integrated Cancer Biology Division, Rajiv Gandhi Centre for Biotechnology, Thycaud PO, Thiruvananthapuram, Kerala 695 014, India.
authors.forename: Sathish Kumar
authors.initials: SK
authors.lastname: Maney
authors.forename: Ann Mary
authors.initials: AM
authors.lastname: Johnson
authors.forename: A
authors.initials: A
authors.lastname: Sampath Kumar
authors.forename: Vineet
authors.initials: V
authors.lastname: Nair
authors.forename: T R
authors.initials: TR
authors.lastname: Santhosh Kumar
authors.forename: C C
authors.initials: CC
authors.lastname: Kartha
mesh_terms: D000818:Animals; D000970:Antineoplastic Agents / Q000633:toxicity*; D017209:Apoptosis / Q000187:drug effects*; D002166:Camptothecin / Q000633:toxicity; D002460:Cell Line; D004305:Dose-Response Relationship, Drug; D004317:Doxorubicin / Q000633:toxicity; D004699:Endocardium / Q000187:drug effects* / Q000473:pathology; D042783:Endothelial Cells / Q000187:drug effects* / Q000473:pathology; D059585:G1 Phase Cell Cycle Checkpoints / Q000187:drug effects; D061307:Human Umbilical Vein Endothelial Cells / Q000187:drug effects / Q000473:pathology; D006801:Humans; D053078:Membrane Potential, Mitochondrial / Q000187:drug effects; D059807:S Phase Cell Cycle Checkpoints / Q000187:drug effects; D013552:Swine; D019284:Thapsigargin / Q000633:toxicity
chemical_list: D000970:Antineoplastic Agents; D019284:Thapsigargin; D004317:Doxorubicin; D002166:Camptothecin