Apoptosis and nuclear levels of p53 protein and proliferating cell nuclear antigen in human hepatoma cells cultured with tumor promoters.
Anticancer drugs etoposide and mitomycin C increased nuclear p53 protein and decreased proliferating cell nuclear antigen (PCNA) of PLC/PRF/5 human hepatoma cells. These changes were followed by DNA fragmentation and apoptosis. Teleocidin antagonized both apoptosis and alterations of nuclear p53 protein and PCNA induced by these anticancer drugs. In contrast, thapsigargin antagonized only drug-induced nuclear accumulation of p53 protein. Therefore, the inhibition of apoptosis appears not to be the common mechanism of tumor promotion. Both tumor promoters suppressed the increase in nuclear p53 protein, suggesting that an inadequate DNA repair due to the reduced nuclear accumulation of p53 protein might be playing important role in enhancing carcinogenesis.
Kaneko
Y
Y
First Department of Medicine, University of Tokyo, Japan.
Tsukamoto
A
A
D017209:Apoptosis / Q000187:drug effects*; D002273:Carcinogens / Q000494:pharmacology*; D006528:Carcinoma, Hepatocellular / Q000378:metabolism*; D004249:DNA Damage; D005047:Etoposide / Q000494:pharmacology; D005434:Flow Cytometry; D006801:Humans; D008235:Lyngbya Toxins / Q000494:pharmacology*; D016685:Mitomycin / Q000494:pharmacology; D018809:Proliferating Cell Nuclear Antigen / Q000378:metabolism*; D013729:Terpenes / Q000494:pharmacology*; D019284:Thapsigargin; D014407:Tumor Cells, Cultured; D016159:Tumor Suppressor Protein p53 / Q000378:metabolism*
D002273:Carcinogens; D008235:Lyngbya Toxins; D018809:Proliferating Cell Nuclear Antigen; D013729:Terpenes; D016159:Tumor Suppressor Protein p53; C022176:teleocidins; D016685:Mitomycin; D019284:Thapsigargin; D005047:Etoposide