Vitamin D analogue: Potent antiproliferative effects on cancer cell lines and lack of hypercalcemic activity

Abstract

The active form of vitamin D3, 1α,25(OH)2D3, plays a major role in maintaining calcium/phosphate homeostasis. In addition, it is a potent antiproliferative and pro-differentiating agent. Unfortunately, it usually causes hypercalcemia in vivo when effective antitumour doses are used. It has therefore been found necessary to synthesise new analogues that retain or even increase the antitumour effects but preclude hypercalcemia. This report presents the synthesis of a novel Gemini vitamin D analogue (UVB1) and its biological evaluation. We demonstrate that this compound has potent antitumoural effects over a wide panel of tumour cell lines while showing lack of hypercalcemic activity and toxicity effects in in vivo assays. The synthesis and biological evaluation of a new Gemini vitamin D analogue, called UVB1, is described. This compound is shown to be a potent antiproliferative vitamin D analogue over a wide panel of tumor cell lines. It also inhibits cellular migration of murine and human cancer cell lines while showing a lack of hypercalcemic and toxicity effects in in vivo assays.