Protein kinase C-dependent anti-apoptotic mechanism that is associated with high sensitivity to anti-Fas antibody in ovarian cancer cell lines.
We compared the sensitivities to apoptosis via anti-Fas antibody of two human ovarian cancer cell lines, NOS4 and SKOV-3, both of which strongly express the Fas antigen on their cell surface. Treatment with anti-Fas antibody induced extensive DNA fragmentation in NOS4 cells but none in SKOV-3 cells. However; both cell lines underwent apoptosis in response to calcium ionophore A23187 or sphingomyelinase, demonstrating that the latter cell line is capable of DNA fragmentation. DNA fragmentation was not induced in either cell line by treatment with PKC activator PMA, however treatment with protein kinase C (PKC) inhibitor H-7 induced extensive DNA fragmentation in NOS4 cells, but again none in SKOV-3 cells. Protein kinase A inhibitor HA1004 treatment did not induce DNA fragmentation in either cell line. Correspondingly, treatment of cells with PMA before anti-Fas antibody or A23187 treatment partially inhibited induction of DNA fragmentation in NOS4 cells but not in SKOV-3 cells. Both NOS4 and SKOV-3 cell lines expressed isozymes of PKC at comparable levels. These results suggest the presence of a PKC-dependent anti-apoptotic mechanism in association with high sensitivity to anti-Fas antibody in these ovarian cancer cell lines.
Equipment Center for Research and Education, Nagoya University School of Medicine, Japan.
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Hayakawa
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Yokoyama
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Tajiri
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T
Okamoto
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Nakashima
D019307:1-(5-Isoquinolinesulfonyl)-2-Methylpiperazine / Q000494:pharmacology; D000906:Antibodies / Q000494:pharmacology*; D017209:Apoptosis; D000001:Calcimycin / Q000494:pharmacology; D002455:Cell Division / Q000187:drug effects; D002518:Ceramides / Q000096:biosynthesis; D017868:Cyclic AMP-Dependent Protein Kinases / Q000037:antagonists & inhibitors; D053938:DNA Fragmentation / Q000187:drug effects; D004791:Enzyme Inhibitors / Q000494:pharmacology; D005260:Female; D005434:Flow Cytometry; D006801:Humans; D007546:Isoquinolines / Q000494:pharmacology; D010051:Ovarian Neoplasms / Q000378:metabolism* / Q000473:pathology; D011493:Protein Kinase C / Q000037:antagonists & inhibitors / Q000378:metabolism*; D015398:Signal Transduction / Q000187:drug effects; D013108:Sphingomyelin Phosphodiesterase / Q000494:pharmacology; D013449:Sulfonamides; D013755:Tetradecanoylphorbol Acetate / Q000494:pharmacology; D013778:Tetrazolium Salts / Q000378:metabolism; D013844:Thiazoles / Q000378:metabolism; D014407:Tumor Cells, Cultured; D019014:fas Receptor / Q000096:biosynthesis / Q000276:immunology
D000906:Antibodies; D002518:Ceramides; D004791:Enzyme Inhibitors; D007546:Isoquinolines; D013449:Sulfonamides; D013778:Tetrazolium Salts; D013844:Thiazoles; D019014:fas Receptor; D000001:Calcimycin; D019307:1-(5-Isoquinolinesulfonyl)-2-Methylpiperazine; C043204:N-(2-guanidinoethyl)-5-isoquinolinesulfonamide; D017868:Cyclic AMP-Dependent Protein Kinases; D011493:Protein Kinase C; D013108:Sphingomyelin Phosphodiesterase; C022616:thiazolyl blue; D013755:Tetradecanoylphorbol Acetate