1,25-Dihydroxyvitamin D3-induced growth restriction of cultured epithelial cells derived from a murine hepatic tumor☆

Abstract Recent evidence suggests that 1,25-dihydroxyvitamin D 3 can accumulate in certain presumed non-target tissues, although the mechanism of action of the vitamin in such cells is not understood. Exposure of 77-1/3a mouse hepatic tumor cells, which derived from a non-target tissue of vitamin D action, to 1,25-dihydroxyvitamin D 3 in chemically-defined serum-free medium resulted in a dose-dependent decline in cellular growth rate and maximal culture population density but did not adversely affect cell viability. Culture of 77-1/3a cells in defined medium containing 10 −7 or 10 −6 M 1,25-dihydroxyvitamin D 3 for 150 hr reduced the growth rate to 64 and 50% of control values respectively. Albumin secretion was unaffected by 1,25-dihydroxyvitamin D 3 exposure; in contrast, the cellular content of the proliferation-associated protein p35 was reduced by 39%, a decline similar in trend and degree to that observed in other tumor cells exposed to differentiation-inducing agents. It appears that 1,25-dihydroxyvitamin D 3 regulates cellular p35 content (within a specific restricted range) as a consequence of proliferative perturbation, rather than differentiated status, of cultured hepatic tumor cells.