Antiproliferative Effect of 13-cis-Retinoic Acid is Associated with Granulocyte Differentiation and Decrease in Cyclin B1 and Bcl-2 Protein Levels in G0/G1 Arrested HL-60 Cells

Abstract

Retinoic acid (RA), similar to specific growth factors, can induce differentiation of proliferating promyelocytic precursors into terminally differentiated granulocytes, although little is known about effects of its 13-cis isomer on promyelocytic leukemia (PML). In this study we demonstrate that 13-cis-RA has a dose and time-dependant antiproliferative effect on HL-60 PML cell line, that it induces cell accumulation in resting G0/G1 phase of the cell cycle followed by an increase in CD11b granulocyte differentiation antigen expression. The obtained increase in the percentage of HL-60 cells in G0/G1 phase and complementary decrease in S phase of the cell cycle are accompanied by a decrease in the expression of cell cycle regulatory molecule cyclin B1. We also show the induction of interferon regulatory factor-I (IRF- I) transcription that can, also, to some extent contribute to the antiproliferative effect of l 3-cis-RA. Furthermore, down-regulation of BcI-2 protein expression in I 3-cis-RA treated HL-60 cells may contribute to sensitivity to apoptosis of growth arrested HL-60 promyelocytic cells.