alpha-Tocopherol inhibits 12-O-tetradecanoyl-phorbol-13-acetate-stimulated deacylation of cellular lipids, prostaglandin production, and changes in cell morphology of Madin-Darby canine kidney cells.
Incubation of the tumor-promoting phorbol diester, 12-O-tetradecanoyl-phorbol-13-acetate with Madin-Darby canine kidney cells (MDCK) stimulated deacylation of phospholipids, prostaglandin production and altered cell morphology. alpha-Tocopherol, if present during the incubation, inhibited these effects. For inhibition, alpha-tocopherol had to be present during incubation of 12-O-tetradecanoyl-phorbol-13-acetate and cells; pretreatment or posttreatment of the cells with alpha-tocopherol was not effective. Inhibition of the 12-O-tetradecanoyl-phorbol-13-acetate effects was specific for the tumor promoter extracted from the Croton tiglium L. plant of the family Euphorbiaceae. Stimulated prostaglandin production by another tumor promotor (phorbol-12, 13-didecanoate), a semisynthetic product of that plant, was also inhibited by alpha-tocopherol. But that of structurally related diterpenoid esters isolated from plants of the family Thymelaeaceae, such as mezerein, gnidimacrin, gnilatimacrin, and gnilatimacrin-20-palmitate, were not. Stimulation of prostaglandin production in MDCK cells by compounds such as benzo(a)pyrene, adriamycin and 17 beta-estradiol or even the basal synthetic activity of MDCK cells was not affected by alpha-tocopherol.
D000818:Animals; D002478:Cells, Cultured; D004285:Dogs; D004305:Dose-Response Relationship, Drug; D007668:Kidney / Q000378:metabolism; D007680:Kidney Neoplasms / Q000139:chemically induced*; D010703:Phorbol Esters / Q000037:antagonists & inhibitors*; D010704:Phorbols / Q000037:antagonists & inhibitors*; D010743:Phospholipids / Q000378:metabolism; D011453:Prostaglandins / Q000096:biosynthesis; D014810:Vitamin E / Q000494:pharmacology*
D010703:Phorbol Esters; D010704:Phorbols; D010743:Phospholipids; D011453:Prostaglandins; D014810:Vitamin E