Effect of bryostatin 1 on drug-induced, topoisomerase II-mediated DNA cleavage and topoisomerase II gene expression in human leukemia cells.
Unlike PMA, bryostatin 1 has been found to have a minimal effect on drug-induced topoisomerase II-mediated DNA cleavage and no effect on topoisomerase II mRNA levels. Furthermore, bryostatin 1 overcame the down-regulatory effects of PMA treatment on (1) drug-induced, topoisomerase II-mediated DNA cleavage, (2) drug-induced cytotoxicity, and (3) topoisomerase II gene expression. Thus, it is unlikely that the effects of phorbol ester treatment on topoisomerase II-mediated events are a direct consequence of protein kinase C activation per se. Rather, the results with bryostatin 1 suggest that the phorbol ester effects are related to more distal effects of phorbol ester treatment that may be related to monocytoid differentiation.
Zwelling
L A
LA
Department of Medical Oncology, University of Texas M.D. Anderson Cancer Center, Houston.
Chan
D
D
Altschuler
E
E
Mayes
J
J
Hinds
J
J
Pettit
G R
GR
D054713:Bryostatins; D004247:DNA / Q000378:metabolism*; D004264:DNA Topoisomerases, Type I / Q000378:metabolism*; D004250:DNA Topoisomerases, Type II / Q000235:genetics / Q000378:metabolism*; D004789:Enzyme Activation / Q000187:drug effects; D015971:Gene Expression Regulation, Enzymologic / Q000187:drug effects; D006801:Humans; D007783:Lactones / Q000494:pharmacology*; D007938:Leukemia / Q000201:enzymology* / Q000235:genetics; D018942:Macrolides; D010703:Phorbol Esters / Q000494:pharmacology; D011493:Protein Kinase C / Q000378:metabolism; D012333:RNA, Messenger / Q000032:analysis; D014407:Tumor Cells, Cultured / Q000187:drug effects
D054713:Bryostatins; D007783:Lactones; D018942:Macrolides; D010703:Phorbol Esters; D012333:RNA, Messenger; C046785:bryostatin 1; D004247:DNA; D011493:Protein Kinase C; D004264:DNA Topoisomerases, Type I; D004250:DNA Topoisomerases, Type II