Paclitaxel-induced apoptosis in HeLa cells is serum dependent.
Exposure of HeLa cells to different concentrations of the antineoplastic drug paclitaxel resulted in a loss of cell viability that was dependent on the concentration and time of exposure to the drug. This phenomenon was associated with the appearance of nuclear morphology typical of apoptosis and DNA breakage into a "ladder" pattern of discrete fragments of nucleosomal size. The induction of cell death was dependent on the serum concentration of the culture media, repressed by pretreatment with a cAMP-dependent protein kinase (PKA) inhibitor, and enhanced by increasing the cell proliferation with previous exposure to a cAMP-analog and a protein kinase-C (PKC) inducer. The proliferative index modifies the effect of taxol on HeLa cells, probably by means of a more rapid accumulation of cells in the G2/M cycle blockage point, although a direct participation of PKA and PKC should not be excluded.
Maldonado
V
V
Laboratorio de Biología Molecular, Instituto Nacional de Cancerología, Mexico City, Mexico.
De Anda
J
J
Meléndez-Zajgla
J
J
D000972:Antineoplastic Agents, Phytogenic / Q000633:toxicity*; D017209:Apoptosis / Q000187:drug effects*; D002455:Cell Division / Q000187:drug effects; D002470:Cell Survival / Q000187:drug effects; D003470:Culture Media; D000242:Cyclic AMP / Q000031:analogs & derivatives / Q000494:pharmacology; D017868:Cyclic AMP-Dependent Protein Kinases / Q000037:antagonists & inhibitors; D004249:DNA Damage; D053938:DNA Fragmentation / Q000187:drug effects; D004305:Dose-Response Relationship, Drug; D004587:Electrophoresis, Agar Gel; D004790:Enzyme Induction / Q000187:drug effects; D006367:HeLa Cells / Q000166:cytology / Q000187:drug effects*; D006801:Humans; D008970:Molecular Weight; D009707:Nucleosomes / Q000187:drug effects; D017239:Paclitaxel / Q000633:toxicity*; D011493:Protein Kinase C / Q000096:biosynthesis; D013873:Thionucleotides / Q000494:pharmacology
D000972:Antineoplastic Agents, Phytogenic; D003470:Culture Media; D009707:Nucleosomes; D013873:Thionucleotides; C015929:8-((4-chlorophenyl)thio)cyclic-3',5'-AMP; D000242:Cyclic AMP; D017868:Cyclic AMP-Dependent Protein Kinases; D011493:Protein Kinase C; D017239:Paclitaxel