Differential modulation of cell cycle, apoptosis and PPARgamma2 gene expression by PPARgamma agonists ciglitazone and 9-hydroxyoctadecadienoic acid in monocytic cells.
We sought to compare the effects of the thiazolidinedione ciglitazone with the endogenous fatty acid PPARgamma agonists 9- and 13-hydroxyoctadecadienoic acid (9- and 13-HODE), in U937 monocytic cells. Ciglitazone and 9-HODE inhibited cell proliferation and all three agonists increased cellular content of C18:0 fatty acids. Ciglitazone and 13-HODE resulted in an increased percentage of cells in S phase and ciglitazone reduced the percentage of cells in G2/M phase of cell cycle, whilst 9-HODE increased the percentage of cells in G0/1 and reduced the fraction in S and G2/M phases. 9-HODE selectively induced apoptosis in U937 cells, and increased PPARgamma2 gene expression. Induction of apoptosis by 9-HODE was not abrogated by the presence of the PPARgamma antagonist GW9662. Synthetic (TZD) and endogenous fatty acid ligands for PPARgamma, ciglitazone and 9- and 13-HODE, possess differential, ligand specific actions in monocytic cells to regulate cell cycle progression, apoptosis and PPARgamma2 gene expression.
Hampel
Jade K A
JK
School of Medicine and Pharmacology, University of Western Australia, Fremantle and Royal Perth Hospitals, Australia.
Brownrigg
Leon M
LM
Vignarajah
Dayalan
D
Croft
Kevin D
KD
Dharmarajan
Arun M
AM
Bentel
Jacqueline M
JM
Puddey
Ian B
IB
Yeap
Bu B
BB
D000813:Anilides / Q000494:pharmacology; D000818:Animals; D000970:Antineoplastic Agents / Q000494:pharmacology; D017209:Apoptosis / Q000187:drug effects*; D002453:Cell Cycle / Q000187:drug effects; D018797:Cell Cycle Proteins / Q000378:metabolism; D002454:Cell Differentiation / Q000187:drug effects; D002460:Cell Line; D002470:Cell Survival / Q000187:drug effects; D015870:Gene Expression / Q000187:drug effects; D006801:Humans; D007004:Hypoglycemic Agents / Q000494:pharmacology; D008041:Linoleic Acids / Q000494:pharmacology; D044243:Linoleic Acids, Conjugated / Q000494:pharmacology*; D009000:Monocytes / Q000166:cytology / Q000187:drug effects* / Q000378:metabolism; D047495:PPAR gamma / Q000819:agonists* / Q000235:genetics / Q000378:metabolism; D045162:Thiazolidinediones / Q000494:pharmacology*; D014157:Transcription Factors / Q000819:agonists / Q000037:antagonists & inhibitors / Q000378:metabolism; D020298:U937 Cells
C457499:2-chloro-5-nitrobenzanilide; D000813:Anilides; D000970:Antineoplastic Agents; D018797:Cell Cycle Proteins; D007004:Hypoglycemic Agents; D008041:Linoleic Acids; D044243:Linoleic Acids, Conjugated; D047495:PPAR gamma; D045162:Thiazolidinediones; D014157:Transcription Factors; C024347:9-hydroxy-10,12-octadecadienoic acid; C024348:13-hydroxy-9,11-octadecadienoic acid; C039671:ciglitazone