AN INHIBITORY EFFECT OF 1α, 25-DIHYDROXYVITAMIN D₃ ON THE GROWTH OF THE RECEPTOR-CONTAINING HUMAN RENAL CARCINOMA CELL LINES

Abstract

We studied the effect of vitamin D₃ compounds on the growth of the human renal carcinoma cell lines, KU-2 and Caki-1, and discovered a receptor protein specific for the active form of vitamin D₃, 1α, 25-dihydroxyvitamin D₃ in the cytosol of these cells. Vitamin D₃ derivatives dose-dependently suppressed proliferation of these cells in a monolayer culture and also suppressed their clonogenicity in a soft agar culture. Radioreceptor assay and sucrose density gradient analysis showed that these two cell lines contained a 3.2S receptor protein to which 1α, 25-dihydroxyvitamin D₃ was specifically bound and which is identical to the receptor in the normal tissues reported previously. The binding capacity was 87fmol/mg protein in the KU-2 cells and was 17fmol/mg protein in the Caki-1 cells. Of the vitamin D derivatives tested, 1α, 25-dihydroxyvitamin D₃ was the most potent in inhibiting KU-2 cell growth, followed by 1α, 24R, 25-trihydroxyvitamin D₃, 25-hydroxyvitamin D₃, 1α-hydroxyvitamin D₃ and 24R, 25-dihydroxyvitamin D₃ in this order. The affinity of various vitamin D₃ derivatives to the KU-2 cytosol receptors was closely related to the abiliry to inhibit growth of the cells. These results indicate that the effects of vitamin D₃ derivatives in inhibiting proliferation and clonogenicity of the cell lines are mediated by the receptor, and that the active form of vitamin D may be one of the regulatory factors affecting the proliferation and other biological functions of renal cell carcinoma.