Cisplatin-induced apoptosis of HeLa cells. Effect of RNA and protein synthesis inhibitors, Ca2+ chelators and zinc.
HeLa cells exposed to cisplatin undergo cell death, presenting morphological and biochemical characteristics typical of apoptosis. In this study we demonstrate that this process is independent of RNA and protein synthesis, since it was not inhibited by actinomycin D or cycloheximide. These substances induced apoptosis by themselves, suggesting an unidentified short-lived inhibitor. The presence of Ca2+ chelators (EDTA and EGTA) did not have effect in this process, excluding the participation of extracellular Ca2+ access. Finally, zinc ions inhibited the low molecular weight DNA degradation and the apoptotic bodies production, but not cell death. These results provide an insight into the mechanism of action of one of the most used antineoplastic drug.
Velázquez
M
M
Division de Investigación Básica. Instituto Nacional de Cancerología, México DF, Mexico.
Maldonado
V
V
Melendez-Zajgla
J
J
D017209:Apoptosis / Q000187:drug effects* / Q000502:physiology; D002118:Calcium / Q000378:metabolism*; D002470:Cell Survival / Q000187:drug effects; D002614:Chelating Agents / Q000494:pharmacology*; D002945:Cisplatin / Q000494:pharmacology*; D003513:Cycloheximide / Q000494:pharmacology; D004247:DNA / Q000187:drug effects / Q000302:isolation & purification / Q000378:metabolism; D003609:Dactinomycin / Q000494:pharmacology; D004492:Edetic Acid / Q000494:pharmacology; D004533:Egtazic Acid / Q000494:pharmacology; D006367:HeLa Cells; D006801:Humans; D007700:Kinetics; D019384:Nucleic Acid Synthesis Inhibitors / Q000494:pharmacology*; D011500:Protein Synthesis Inhibitors / Q000494:pharmacology*; D012313:RNA / Q000096:biosynthesis*; D015032:Zinc / Q000494:pharmacology*
D002614:Chelating Agents; D019384:Nucleic Acid Synthesis Inhibitors; D011500:Protein Synthesis Inhibitors; D003609:Dactinomycin; D004533:Egtazic Acid; D012313:RNA; D004247:DNA; D003513:Cycloheximide; D004492:Edetic Acid; D015032:Zinc; D002945:Cisplatin; D002118:Calcium