Combined effect of sodium selenite and campthotecin on cervical carcinoma cells.
The effects of selenite, campthotecin and their combination were investigated in cervical carcinoma cell line Hep-2 HeLa during 24h. The measured parameters included morphological changes, proliferation, oxidative stress, mitochondrial status, caspase-3 activation and nuclear fragmentation. Selenite at all but lowest concentrations inhibited cell growth and proliferation and induced cell death characterized by membrane blebbing, oxidative stress and mitochondrial damage, occurring in the absence of caspase-3 activation and nuclear fragmentation. Campthotecin at all concentrations induced gradual apoptosis including all measured morphological and molecular parameters with exception of oxidative stress. A combination of selenite and campthotecin induced both antagonistic and synergistic effects on cervical carcinoma cells. While low selenium concentration slightly reduced cytotoxicity and proapoptotic effects of campthotecin, moderate and higher concentrations of selenium enhanced them, changing simultaneously apoptosis into more necrosis-like death. These results show importance of selenium as a potential modulator and enhancer of campthotecin-based anticancer therapy in nonovarian malignancies.
Rudolf
E
E
Department of Medical Biology and Genetics, Charles University, Prague, Faculty of Medicine, Hradec Králové, Czech Republic. rudolf@lfhk.cuni.cz
Radocha
J
J
Cervinka
M
M
Cerman
J
J
D000971:Antineoplastic Combined Chemotherapy Protocols / Q000627:therapeutic use*; D017209:Apoptosis; D002166:Camptothecin / Q000008:administration & dosage*; D002277:Carcinoma / Q000188:drug therapy*; D053148:Caspase 3; D020169:Caspases / Q000378:metabolism; D002455:Cell Division; D045744:Cell Line, Tumor; D002467:Cell Nucleus / Q000378:metabolism; D053938:DNA Fragmentation; D004305:Dose-Response Relationship, Drug; D004789:Enzyme Activation; D005260:Female; D006367:HeLa Cells; D006801:Humans; D008928:Mitochondria / Q000473:pathology; D018384:Oxidative Stress; D018038:Sodium Selenite / Q000008:administration & dosage*; D013997:Time Factors; D002583:Uterine Cervical Neoplasms / Q000188:drug therapy*
C505407:CASP3 protein, human; D053148:Caspase 3; D020169:Caspases; D018038:Sodium Selenite; D002166:Camptothecin