Responsiveness of human carcinoma cells of gynecologic origin to 1,25-dihydroxycholecalciferol.
In responsive tissues the induction of 25-hydroxycholecalciferol 24-hydroxylase activity is a marker of 1,25-dihydroxycholecalciferol action. In this study we investigated the responsiveness of various malignant cells, which were derived from carcinomas of gynecologic origin, to 1,25-dihydroxycholecalciferol; we did so because it has been demonstrated that replication of certain malignant human cells that are 1,25-dihydroxycholecalciferol-responsive is inhibited by treatment with this substance. We found that 1,25-dihydroxycholecalciferol treatment caused an increase in 25-hydroxycholecalciferol 24-hydroxylase activity in gynecologic carcinoma cells that were maintained in monolayer culture. The cells were established from ovarian, endometrial, cervical, and vaginal neoplasms. After treatment with 1,25-dihydroxycholecalciferol (10 nmol/L) for 18 hours, the specific activity of 25-hydroxycholecalciferol 24-hydroxylase increased between 2,4- and 49-fold in these cells. This increase in 25-hydroxycholecalciferol 24-hydroxylase activity is suggestive that certain gynecologic malignancies are responsive to 1,25-dihydroxycholecalciferol. We also found, however, that 1,25-dihydroxycholecalciferol did not act to decrease the rate of replication of these cells; indeed in ovarian adenocarcinoma cells, 1,25-dihydroxycholecalciferol caused a decrease in doubling time; in the other cells of this study, there was no effect of 1,25-dihydroxycholecalciferol on cell replication.
D000230:Adenocarcinoma / Q000473:pathology*; D002117:Calcitriol / Q000494:pharmacology*; D002294:Carcinoma, Squamous Cell / Q000473:pathology*; D003577:Cytochrome P-450 Enzyme System; D004790:Enzyme Induction; D005260:Female; D005833:Genital Neoplasms, Female / Q000473:pathology*; D006801:Humans; D013250:Steroid Hydroxylases / Q000378:metabolism*; D014410:Tumor Stem Cell Assay; D065668:Vitamin D3 24-Hydroxylase
D003577:Cytochrome P-450 Enzyme System; D013250:Steroid Hydroxylases; D065668:Vitamin D3 24-Hydroxylase; D002117:Calcitriol