Induction of PPARgamma1 expression in human THP-1 monocytic leukemia cells by 9-cis-retinoic acid is associated with cellular growth suppression.
9-cis-Retinoic acid (RA) and peroxisome proliferator activated receptor gamma (PPARgamma) regulates cellular growth and differentiation. In THP-1 cells, a human monocytic leukemia cell line, RA markedly induced PPARgamma1 RNA, nuclear PPARgamma1 protein and suppressed cell growth. The PPARgamma ligand, BRL49653 enhanced RA's growth suppression ability. With BRL49653 alone, THP-1 cell growth was only marginally suppressed. Cell cycle analysis revealed the G1 phase cell population was significantly increased when cells were treated with both ligands. RA induced growth suppression did not differentiate the THP-1 cells to macrophages. Phorbol ester (PMA) induced differentiation of cells to macrophage also induced PPARgamma1 expression, however when RA is given either simultaneously or sequentially to these cells, no further increase in expression of the nuclear receptor was observed. Overall, these data suggest RA induction of PPARgamma1 may block cell growth and may have application for the treatment of proliferative diseases.
Zhu
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L
Parke-Davis Pharmaceutical Research, Division of Warner-Lambert Company, 2800 Plymouth Road, Ann Arbor, Michigan, 48105, USA.
Gong
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B
Bisgaier
C L
CL
Aviram
M
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Newton
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RS
D000077556:Alitretinoin; D000970:Antineoplastic Agents / Q000494:pharmacology; D002455:Cell Division / Q000187:drug effects; D006801:Humans; D007536:Isomerism; D007951:Leukemia, Myeloid / Q000378:metabolism*; D018160:Receptors, Cytoplasmic and Nuclear / Q000096:biosynthesis*; D014157:Transcription Factors / Q000096:biosynthesis*; D014212:Tretinoin / Q000494:pharmacology*; D014407:Tumor Cells, Cultured
D000970:Antineoplastic Agents; D018160:Receptors, Cytoplasmic and Nuclear; D014157:Transcription Factors; D000077556:Alitretinoin; D014212:Tretinoin