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.
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-dependent 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-1 (IRF-1) transcription that can, also, to some extent contribute to the antiproliferative effect of 13-cis-RA. Furthermore, down-regulation of Bcl-2 protein expression in 13-cis-RA treated HL-60 cells may contribute to sensitivity to apoptosis of growth arrested HL-60 promyelocytic cells.
Vuletic
Ana
A
Institute for Oncology and Radiology of Serbia, Beograd, Serbia. radovanovica@ncrc.ac.rs
Konjevic
Gordana
G
Milanovic
Desanka
D
Ruzdijic
Sabera
S
Jurisic
Vladimir
V
D000970:Antineoplastic Agents / Q000494:pharmacology*; D015153:Blotting, Western; D002453:Cell Cycle / Q000187:drug effects; D002454:Cell Differentiation / Q000187:drug effects; D049109:Cell Proliferation / Q000187:drug effects*; D002469:Cell Separation; D056744:Cyclin B1 / Q000096:biosynthesis*; D005434:Flow Cytometry; D006098:Granulocytes / Q000166:cytology* / Q000187:drug effects; D018922:HL-60 Cells; D006801:Humans; D015474:Isotretinoin / Q000494:pharmacology*; D019253:Proto-Oncogene Proteins c-bcl-2 / Q000096:biosynthesis*; D020133:Reverse Transcriptase Polymerase Chain Reaction
D000970:Antineoplastic Agents; D056744:Cyclin B1; D019253:Proto-Oncogene Proteins c-bcl-2; D015474:Isotretinoin