Differential regulation of P53, c-Myc, Bcl-2, Bax and AFP protein expression, and caspase activity during 10-hydroxycamptothecin-induced apoptosis in Hep G2 cells.
10-Hydroxycamptothecin (HCPT), a DNA topoisomerase I (Topo I) inhibitor, exhibited a remarkable apoptosis-inducing effect on human hepatoma Hep G2 cells. We studied the effect of HCPT upon the expression of P53, c-Myc, Bcl-2, Bax and alpha-fetoprotein (AFP) proteins, and caspase (caspase-1 and caspase-3) activity of Hep G2 cells. It showed that HCPT at a dose of 0.1 microg/ml increased the expression of P53, c-Myc and Bax protein, and decreased the expression of Bcl-2 and AFP. The increase of P53, which was remarkable after only 3 h incubation with HCPT, occurred much earlier than the changes of other proteins, suggesting that the increase of P53 expression may be the upstream event in the apoptosis of Hep G2 cells induced by HCPT. Both caspase-1 and caspase-3 were activated in Hep G2 cells by HCPT treatment, suggesting that caspase-1 and caspase-3 are involved in the process of apoptosis in Hep G2 cells, and may be the main effectors of the apoptosis.
Zhang
X W
XW
Divison of Cancer Pharmacology, Shanghai Institue of Materia Medica, Shanghai Institutes for Biological Sciences, Chinese Academy of Science.
Xu
B
B
D000972:Antineoplastic Agents, Phytogenic / Q000494:pharmacology*; D017209:Apoptosis / Q000187:drug effects* / Q000502:physiology; D002166:Camptothecin / Q000031:analogs & derivatives* / Q000494:pharmacology*; D006528:Carcinoma, Hepatocellular / Q000201:enzymology / Q000378:metabolism*; D020170:Caspase 1 / Q000378:metabolism; D053148:Caspase 3; D020169:Caspases / Q000378:metabolism*; D005434:Flow Cytometry; D015972:Gene Expression Regulation, Neoplastic; D006801:Humans; D008113:Liver Neoplasms / Q000201:enzymology / Q000378:metabolism*; D011518:Proto-Oncogene Proteins / Q000096:biosynthesis*; D019253:Proto-Oncogene Proteins c-bcl-2 / Q000096:biosynthesis; D016271:Proto-Oncogene Proteins c-myc / Q000096:biosynthesis; D014407:Tumor Cells, Cultured; D016159:Tumor Suppressor Protein p53 / Q000096:biosynthesis*; D000509:alpha-Fetoproteins / Q000096:biosynthesis; D051028:bcl-2-Associated X Protein
D000972:Antineoplastic Agents, Phytogenic; C494826:BAX protein, human; D011518:Proto-Oncogene Proteins; D019253:Proto-Oncogene Proteins c-bcl-2; D016271:Proto-Oncogene Proteins c-myc; D016159:Tumor Suppressor Protein p53; D000509:alpha-Fetoproteins; D051028:bcl-2-Associated X Protein; C028098:10-hydroxycamptothecin; C505407:CASP3 protein, human; D053148:Caspase 3; D020169:Caspases; D020170:Caspase 1; D002166:Camptothecin