Diacylglycerols enhance the anti-tumor effect of glucocorticoid on L5178Y lymphoblasts in vivo.
1,2-Dioleoyl-rac-glycerol, a potent activator of protein kinase C, was found to enhance the growth-inhibitory effect of triamcinolone acetonide on L5178Y lymphoblasts in adrenalectomized, male DBA/2 mice. On the other hand, in mice without adrenalectomy, it markedly inhibited tumor growth without increasing the plasma level of corticosterone or adrenocorticotropic hormone or reducing the body weight. These results suggest that diacylglycerol enhances the action of endogenous glucocorticoid to a sufficient level to inhibit the growth of lymphoblasts. Of various diacylglycerols with different carbon chain lengths tested, 1,2-dioleoyl-rac-glycerol was the most potent growth inhibitor and was maximally effective at a dose of above 30 micrograms/100 g body weight. This finding suggests that diacylglycerols may be useful for enhancing the antitumor effect of a low dose of glucocorticoid or endogenous glucocorticoid on lymphoblasts without any significant side effect.
Fukusen
N
N
Division of Enzyme Chemistry, University of Tokushima.
Kido
H
H
Kato
Y
Y
Ishidoh
K
K
Katunuma
N
N
D000315:Adrenalectomy; D000324:Adrenocorticotropic Hormone / Q000097:blood; D000818:Animals; D000971:Antineoplastic Combined Chemotherapy Protocols / Q000627:therapeutic use; D003345:Corticosterone / Q000097:blood; D004075:Diglycerides / Q000008:administration & dosage / Q000627:therapeutic use*; D004789:Enzyme Activation / Q000187:drug effects; D005989:Glycerides / Q000627:therapeutic use*; D008214:Lymphocytes; D008297:Male; D051379:Mice; D008811:Mice, Inbred DBA; D009368:Neoplasm Transplantation; D009374:Neoplasms, Experimental / Q000188:drug therapy* / Q000473:pathology; D011493:Protein Kinase C / Q000378:metabolism; D013755:Tetradecanoylphorbol Acetate / Q000494:pharmacology; D014222:Triamcinolone Acetonide / Q000008:administration & dosage / Q000627:therapeutic use*; D014407:Tumor Cells, Cultured
D004075:Diglycerides; D005989:Glycerides; D000324:Adrenocorticotropic Hormone; D011493:Protein Kinase C; D014222:Triamcinolone Acetonide; D013755:Tetradecanoylphorbol Acetate; D003345:Corticosterone; C013965:diolein