INHIBITION OF PROLIFERATION AND INDUCTION OF MONOCYTIC DIFFERENTIATION IN HL-60 HUMAN PROMYELOCYTIC LEUKEMIA-CELLS TREATED WITH BILE-ACIDS IN-VITRO

We have tested the effect of several bile acids on the proliferation a nd differentiation of the HL60 human promyelocytic leukemia cell line in vitro. Deoxycholate, chenodeoxycholate and lithocholic acid caused dose-dependent inhibition of cell proliferation and induction of diffe rentiation along the monocyte/macrophage pathway as determined by morp hology, NBT test, non-specific esterase, and staining by monoclonal an tibodies against specific cell-surface antigens. Optimal effects were obtained at 100, 75, and 60 mu M of the 3 bile acids respectively. Cel l-cycle flow-cytometric analysis showed that a substantial fraction of HL60 cells accumulated at the G(0)/G(1) transition. Protein-kinase-C inhibitors such as sphinganine and H-7 inhibited the differentiation-i nducing effect of bile acids, suggesting a possible role for PKC in th is regulation. When bile acids were combined with non-effective concen trations of all-trans retinoic acid, enhancement of the monocytic diff erentiation of THP-1 human leukemia cells was observed. Our findings d emonstrate induction of tumor-cell differentiation by bile acids, comp ounds that present minimal undesirable effects in humans. (C) 1994 Wil ey-Liss, Inc.