Antiproliferative effect of 1,25-dihydroxyvitamin D 3 and its analogs on human colon adenocarcinoma cells (CaCo-2): Influence of extracellular calcium

Abstract

Depending on culture in either “low Ca ++” (0.25 mM) or “normal Ca ++” (1.8 mM) medium, human colon adenocarcinoma-derived CaCo-2 cells exhibit differential sensitivity to the antiproliferative action of 1,25-dihydroxyvitamin D 3 (1,25(OH) 2D 3) and of two side-chain modified analogs, 1,25S,26-trihydroxy-Δ22-vitamin D 3 (Ro 23-4319) and 1,25-dihydroxy-Δ16-23yne-vitamin D 3 (Ro 3-7553). CaCo-2 cells cultured under low Ca ++ conditions exhibit a high proliferative potential, and in these cells, all vitamin D compounds under investigation significantly inhibit [ 3H]thymidine incorporation into cellular DNA at ≥10 −10 M. The rank order of biopotency is: Ro 23-7553≥Ro 23-4319 >1,25(OH) 2D 3. At 1.8 mM Ca ++, only Ro 23-7553 is able to inhibit proliferation of CaCo-2 cells. Parallel to their antiproliferative action, all three vitamin D compounds stimulate akaline phosphatase activity in CaCo-2 cells, indicating their ability to induce differentiated functions at the same time as they reduce neoplastic cell growth.