title: Inhibition of proliferation and induction of monocytic differentiation on HL60 human promyelocytic leukemia cells treated with bile acids in vitro.
abstract: We have tested the effect of several bile acids on the proliferation and 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 differentiation along the monocyte/macrophage pathway as determined by morphology, NBT test, non-specific esterase, and staining by monoclonal antibodies against specific cell-surface antigens. Optimal effects were obtained at 100, 75, and 60 microM of the 3 bile acids respectively. Cell-cycle flow-cytometric analysis showed that a substantial fraction of HL60 cells accumulated at the G0/G1 transition. Protein-kinase-C inhibitors such as sphinganine and H-7 inhibited the differentiation-inducing effect of bile acids, suggesting a possible role for PKC in this regulation. When bile acids were combined with non-effective concentrations of all-trans retinoic acid, enhancement of the monocytic differentiation of THP-1 human leukemia cells was observed. Our findings demonstrate induction of tumor-cell differentiation by bile acids, compounds that present minimal undesirable effects in humans.
authors.affiliation: Department of Animal Science, Faculty of Agriculture, Hebrew University of Jerusalem, Rehovot, Israel.
authors.forename: A
authors.initials: A
authors.lastname: Zimber
authors.forename: A
authors.initials: A
authors.lastname: Chedeville
authors.forename: C
authors.initials: C
authors.lastname: Gespach
authors.forename: J P
authors.initials: JP
authors.lastname: Abita
mesh_terms: D019307:1-(5-Isoquinolinesulfonyl)-2-Methylpiperazine; D001647:Bile Acids and Salts / Q000494:pharmacology*; D002453:Cell Cycle; D002454:Cell Differentiation / Q000187:drug effects*; D002455:Cell Division / Q000187:drug effects*; D002635:Chenodeoxycholic Acid / Q000494:pharmacology; D003840:Deoxycholic Acid / Q000494:pharmacology; D005434:Flow Cytometry; D006801:Humans; D007546:Isoquinolines / Q000494:pharmacology; D015473:Leukemia, Promyelocytic, Acute / Q000473:pathology*; D008095:Lithocholic Acid / Q000494:pharmacology; D009000:Monocytes / Q000473:pathology*; D010879:Piperazines / Q000494:pharmacology; D011493:Protein Kinase C / Q000037:antagonists & inhibitors; D013110:Sphingosine / Q000031:analogs & derivatives / Q000494:pharmacology; D014212:Tretinoin / Q000494:pharmacology; D014407:Tumor Cells, Cultured
chemical_list: D001647:Bile Acids and Salts; D007546:Isoquinolines; D010879:Piperazines; D003840:Deoxycholic Acid; D002635:Chenodeoxycholic Acid; D014212:Tretinoin; D008095:Lithocholic Acid; D019307:1-(5-Isoquinolinesulfonyl)-2-Methylpiperazine; D011493:Protein Kinase C; D013110:Sphingosine; C005682:safingol