The role of adenylate cyclase, cAMP and PGE2 in the in vitro growth regulation of murine melanoma cells by vitamin E.
Previous studies have shown that vitamin E supplementation inhibits murine melanoma cell growth in vitro. In this study, malignant murine melanoma (BL6) and non-malignant monkey kidney (LLCMK) cells were supplemented with 1-10 micrograms/ml D-alpha-tocopherol acid succinate (vitamin E succinate). The effect of vitamin E succinate supplementation on growth as well as the levels of adenylate cyclase activity, prostaglandin E2 (PGE2) and cyclic adenosine monophosphate (cAMP) were determined in these cells. Results from these studies indicated a significant inhibition of BL6 cell growth at 5 (P < 0.025), 7 and 10 micrograms/ml (P < 0.001) vitamin E succinate supplementation, while LLCMK cells showed no significant increase or decrease in growth following vitamin E succinate supplementation. BL6 cells supplemented with 7 and 10 micrograms/ml vitamin E succinate showed a marked increase in PGE2 levels, with a significant increase (P < 0.025) occurring at 10 micrograms/ml. Adenylate cyclase activity in BL6 cells was also significantly increased at vitamin E succinate concentrations of 7 (P < 0.05) and 10 micrograms/ml (P < 0.05), respectively, and supplementation of these cells with 5 (P < 0.05), 7 and 10 micrograms/ml (P < 0.001) vitamin E succinate resulted in a significant increase in the levels of cAMP, while LLCMK cells showed no significant increase or decrease in PGE2, adenylate cyclase activity or cAMP levels over the vitamin concentrations tested.
Ottino
P
P
Department of Biochemistry and Microbiology, Rhodes University, Grahamstown, South Africa.
Duncan
J R
JR
D000262:Adenylyl Cyclases / Q000187:drug effects / Q000378:metabolism*; D000818:Animals; D002455:Cell Division / Q000187:drug effects; D002478:Cells, Cultured; D000242:Cyclic AMP / Q000378:metabolism*; D015232:Dinoprostone / Q000378:metabolism*; D000882:Haplorhini; D008545:Melanoma / Q000188:drug therapy* / Q000473:pathology; D051379:Mice; D024505:Tocopherols; D014407:Tumor Cells, Cultured; D014810:Vitamin E / Q000031:analogs & derivatives / Q000494:pharmacology*
D014810:Vitamin E; D000242:Cyclic AMP; D000262:Adenylyl Cyclases; D015232:Dinoprostone; D024505:Tocopherols