Inhibition of phosphorylation of histone H1 and H3 induced by 10-hydroxycamptothecin, DNA topoisomerase I inhibitor, in murine ascites hepatoma cells.
Hydroxycamptothecin (HCPT), isolated from Camptotheca acuminata, is a powerful antitumor alkaloid. Previous studies indicated that the molecular target of this agent was DNA topoisomerase I. The present results demonstrated that in vitro treatment of murine ascites hepatoma cells with HCPT resulted in a marked reduction in DNA syntheses and the inhibition of phosphorylation in histone was in a time-dependent manner. Gel electrophoresis found that HCPT had a selectively inhibitory effect on the phosphorylation of histone H1 and H3, but less effect on the other kinds of histones. In vivo, HCPT also exhibited a suppressive effect on histone H1 and H3 phosphorylation. These data suggested that HCPT-induced cell killing may be, at least in part, associated with the suppression of histone H1 and H3 phosphorylation.
Ling
Y H
YH
Department of pharmacology I, Shanghai Institute of Materia Medica, Chinese Academy of Sciences.
Xu
B
B
D000818:Animals; D000972:Antineoplastic Agents, Phytogenic / Q000494:pharmacology*; D002166:Camptothecin / Q000031:analogs & derivatives* / Q000494:pharmacology; D004273:DNA, Neoplasm / Q000096:biosynthesis; D006657:Histones / Q000378:metabolism*; D008114:Liver Neoplasms, Experimental / Q000378:metabolism* / Q000473:pathology; D051379:Mice; D010766:Phosphorylation / Q000187:drug effects; D059004:Topoisomerase I Inhibitors; D014407:Tumor Cells, Cultured
D000972:Antineoplastic Agents, Phytogenic; D004273:DNA, Neoplasm; D006657:Histones; D059004:Topoisomerase I Inhibitors; C028098:10-hydroxycamptothecin; D002166:Camptothecin