Similarity and dissimilarity between phorbol ester tumor promoters and 1 alpha,25-dihydroxyvitamin D3, an active form of vitamin D3.
During collaborative studies on regulation of differentiation and neoplastic transformation, similarities and dissimilarities were found between the actions of phorbol ester tumor promoters and 1 alpha,25-dihydroxyvitamin D3 (1 alpha,25(OH)2D3), an active form of vitamin D3. Like 12-O-tetradecanoylphorbol-13-acetate (TPA), 1 alpha,25(OH)2D3 stimulates terminal differentiation of M1 and HL-60 myeloid leukemia cells and epidermal keratinocytes, blocks dimethylsulfoxide-induced differentiation of Friend erythroleukemia cells, and enhances chemically induced transformation of BALB 3T3 cells. Unlike TPA, 1 alpha,25(OH)2D3 does not induce ornithine decarboxylase in mouse skin, but inhibits induction of this enzyme by TPA. These actions are all specific for 1 alpha,25(OH)2D3: at least 100 times higher doses of other derivatives of vitamin D3 are required for the same biological effects. A specific cytosol receptor for 1 alpha,25(OH)2D3 was found in these cells, suggesting that this compound has a receptor mediated action. These findings suggest that 1 alpha,25(OH)2D3 may be a natural modulator of growth and differentiation of cells and of promotion of tumor formation.
D000818:Animals; D002117:Calcitriol / Q000633:toxicity*; D002454:Cell Differentiation / Q000187:drug effects; D002471:Cell Transformation, Neoplastic / Q000187:drug effects; D004790:Enzyme Induction; D006801:Humans; D007951:Leukemia, Myeloid / Q000139:chemically induced / Q000473:pathology; D009955:Ornithine Decarboxylase / Q000096:biosynthesis; D010703:Phorbol Esters / Q000633:toxicity*; D010704:Phorbols / Q000633:toxicity*; D012867:Skin / Q000187:drug effects
D010703:Phorbol Esters; D010704:Phorbols; D009955:Ornithine Decarboxylase; D002117:Calcitriol