Phorbol esters potentiate glucocorticoid-induced cytotoxicity in CEM-C7 human T-leukemia cell line.
Phorbol ester tumor promoter, such as 12-O-tetradecanoylphorbol-13-acetate (TPA), is synergistic with dexamethasone to cause growth inhibition of CEM-C7 human T-leukemia cell line. A specific saturable binding component which may mediate the phorbol ester effects has been identified by using [20-(3)H]phorbol 12,13-dibutyrate in a whole cell binding assay. Saturation of the specific binding occurs at a concentration (approx. 100 nM) consistent with causing maximal cytotoxicity. Scatchard analysis of the binding after 15 min at 37 degrees C demonstrates a single class of binding sites. The number is 194,000 sites per cell. Other phorbol esters are also cytotoxic to CEM-C7 cell in the presence of 30 nM dexamethasone in an approximate proportion to their activity in competing for [20-(3)H]phorbol 12,13-dibutyrate binding. Phorbol 12, 13-didecanoate, 4-O-methyl PMA, 4-beta-phorbol do not compete for specific binding. The synergism of phorbol esters and dexamethasone on CEM-C7 cells is reversible by 1-(5-isoquinolinylsulfonyl)-2-methylpiperazine(H-7). However, by treating CEM-C7 cells with TPA for 48 h there is not any increase in the affinity or levels of glucocorticoid receptor. It is tentatively concluded that phorbol esters may play an important role linked to the glucocorticoid-induced growth inhibition in CEM-C7 human T-leukemic cell.
Sato
K
K
Department of Pediatrics, Mie University School of Medicine, Tsu, Japan.
Ido
M
M
Kamiya
H
H
Sakurai
M
M
Hidaka
H
H
D001667:Binding, Competitive; D029742:Caenorhabditis elegans Proteins; D002352:Carrier Proteins; D002460:Cell Line; D002470:Cell Survival / Q000187:drug effects*; D003907:Dexamethasone / Q000378:metabolism / Q000633:toxicity*; D004357:Drug Synergism; D006131:Growth Inhibitors / Q000633:toxicity; D006801:Humans; D007938:Leukemia / Q000378:metabolism / Q000473:pathology*; D015240:Phorbol 12,13-Dibutyrate; D010703:Phorbol Esters / Q000378:metabolism / Q000633:toxicity*; D011493:Protein Kinase C / Q000032:analysis; D011955:Receptors, Drug; D011965:Receptors, Glucocorticoid / Q000187:drug effects; D013329:Structure-Activity Relationship; D013601:T-Lymphocytes / Q000187:drug effects* / Q000378:metabolism / Q000473:pathology
D029742:Caenorhabditis elegans Proteins; D002352:Carrier Proteins; D006131:Growth Inhibitors; D010703:Phorbol Esters; D011955:Receptors, Drug; D011965:Receptors, Glucocorticoid; C028697:dexamethasone receptor; C083141:phorbol ester binding protein; C027776:phorbol ester receptor; D015240:Phorbol 12,13-Dibutyrate; D003907:Dexamethasone; D011493:Protein Kinase C