Effects of vitamin D 3 derivatives on growth, differentiation and apoptosis in tumoral colonic HT 29 cells: possible implication of intracellular calcium

Abstract

In addition to the effects on tumor cell differentiation and growth inhibition, vitamin D 3 derivatives may exert other cellular actions such as the inhibition of angiogenesis or the induction of apoptosis. In this study, we demonstrated that vitamin D 3 derivatives, 1,25-dihydroxyvitamin D 3 the natural derivative and Ro 23-7553, a synthetic derivative, displayed complex effects in tumoral colonic HT 29 cells. Indeed, as a function of the stage of culture, they induced either apoptosis or differentiation along with a constant cell cycle blockade in G1. Intracellular calcium analysis indicated that treatment resulted in disturbance in the distribution of calcium suggesting a possible role for intracellular calcium in the observed effects. The association of 9- cis-retinoic acid, the ligand of RXR, with vitamin D 3 derivatives modified the demonstrated effects, indicating, in our model, a preferential effect of vitamin D 3 derivatives via the heterodimeric form of the receptor.