Vitamin A Research Today is a free monthly online journal that collates and summarizes the latest research about Vitamin A, including details on retinol, benefits, dosage, supplements, deficiency, information.

Enhancing effect of indirubin derivatives on 1,25-dihydroxyvitamin D3- and all-trans retinoic acid-induced differentiation of HL-60 leukemia cells.

Kim SH, Kim SW, Choi SJ, Kim YC, Kim TS

School of Life Sciences and Biotechnology, Korea University, Seoul 136-701, Republic of Korea.

The induction of differentiation represents a new and promising approach to cancer therapy, well illustrated by the treatment of acute promyelocytic leukemia (APL) with 1,25-dihydroxyvitamin D3 [1,25-(OH)2D3] or all-trans retinoic acid (ATRA). Using combinations of low, nontoxic concentrations of either 1,25-(OH)2D3 or ATRA and differentiation-enhancing chemicals, adverse effects such as hypercalcemic effects have been ameliorated, and long-term survival has been improved. Indirubin has been demonstrated to exert anti-leukemic effects in cases of chronic myelocytic leukemia. Previously, we synthesized a series of indirubin derivatives and evaluated their anti-proliferative properties against cancer cells. In this study, we determined the enhancing activities of these derivatives on 1,25-(OH)2D3- and ATRA-induced differentiation of human promyelocytic leukemia HL-60 cells. Importantly, some of these derivatives were found to synergistically enhance the differentiation of HL-60 cells in a concentration-dependent manner when coupled with low doses of either 1,25-(OH)2D3 or ATRA. The ability of indirubin derivatives to enhance the differentiation potential of 1,25-(OH)2D3 or ATRA may improve the ultimate outcomes of APL therapy.

Published 21 August 2006 in Bioorg Med Chem, 14(19): 6752-8.
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