PPARgamma ligands inhibit growth and induce apoptosis of various cancer cells. 4-Hydroxynonenal (HNE), a product of lipid peroxidation, inhibits proliferation and induces differentiation or apoptosis in neoplastic cells. The aim of this work was to investigate the effects of PPARgamma ligands (rosiglitazone and 15-deoxy-prostaglandin J2 (15d-PGJ2)) and HNE, alone or in association, on proliferation, apoptosis, differentiation, and growth-related and apoptosis-related gene expression in colon cancer cells (CaCo-2 cells). PPARgamma ligands inhibited cell proliferation (IC50 was 37.47+/-6.6 microM, for 15d-PGJ2, and 170.34+/-20 microM for rosiglitazone). HNE (1 microM) inhibited cell growth by 70%. Apoptosis was induced by 15d-PGJ2 and HNE and, to a minor extent, rosiglitazone. Differentiation was induced by rosiglitazone and by 15d-PGJ2, but not by HNE. PPARgamma ligands inhibited c-myc expression. HNE induced a transitory increase in c-myc expression and a subsequent down-regulation. HNE induced p21 expression, whereas PPARgamma ligands did not. Expression of the bax gene was increased by HNE and 15d-PGJ2, but not by rosiglitazone. No synergism or antagonism was found between HNE and PPARgamma ligands. Both apoptosis and differentiation induction may be responsible for the inhibition of proliferation by PPARgamma ligands; apoptosis and c-myc and p21 expression seem to be involved in the inhibition of proliferation by HNE.
Download full-text PDF |
Source |
|---|---|
| http://dx.doi.org/10.1016/j.freeradbiomed.2007.02.009 | DOI Listing |
Publication Analysis
Top Keywords
Similar Publications
An alternatively translated isoform of PPARG proposes AF-1 domain inhibition as an insulin sensitization target.
Diabetes
January 2025
Division of Endocrinology and Metabolism, Department of Medicine, University of California, San Diego, La Jolla, CA, USA.
PPARγ is the pharmacological target of thiazolidinediones (TZDs), potent insulin sensitizers that prevent metabolic disease morbidity but are accompanied by side effects such as weight gain, in part due to non-physiological transcriptional agonism. Using high throughput genome engineering, we targeted nonsense mutations to every exon of PPARG, finding an ATG in Exon 2 (chr3:12381414, CCDS2609 c.A403) that functions as an alternative translational start site.
View Article and Find Full Text PDFTriterpenoids from Chios Mastiha Resin Against MASLD-A Molecular Docking Survey.
Curr Issues Mol Biol
January 2025
Department of Pharmacy, Faculty of Medicine, University of Novi Sad, 21000 Novi Sad, Serbia.
Non-alcoholic fatty liver disease (NAFLD) is the most common chronic liver disease without an approved pharmacological approach for its prevention/treatment. Based on the modified Delphi process, NAFLD was redefined as metabolic dysfunction-associated steatotic liver disease (MASLD) to highlight the metabolic aspect of liver pathogenesis. Chios mastiha ( var.
View Article and Find Full Text PDFRevealing rutaecarpine's promise: A pathway to parkinson's disease relief through PPAR modulation.
Int Immunopharmacol
January 2025
Department of Neurosurgery, The Second Affiliated Hospital, Jiangxi Medical College, Nanchang University, Nanchang 330006 Jiangxi, China; Jiangxi Key Laboratory of Neurological Tumors and Cerebrovascular Diseases, Nanchang 330006 Jiangxi, China; Jiangxi Health Commission Key Laboratory of Neurological Medicine, Nanchang 330006 Jiangxi, China; Institute of Neuroscience, Nanchang University, Nanchang 330006 Jiangxi, China. Electronic address:
The pathological mechanisms of Parkinson's disease (PD) is complex, and no definitive cure currently exists. This study identified Rutaecarpine (Rut), an alkaloid extracted from natural plants, as a potential therapeutic agent for PD. To elucidate its mechanisms of action and specific effects in PD, network pharmacology, molecular docking, and experimental validation methods were employed.
View Article and Find Full Text PDFChronic low-dose REV-ERBs agonist SR9009 mitigates constant light-induced weight gain and insulin resistance via adipogenesis modulation.
Biomed J
January 2025
Department of Otolaryngology, Kaohsiung Chang Gung Memorial Hospital and Chang Gung University College of Medicine, Kaohsiung, Taiwan; School of Medicine, College of Medicine, National Sun Yat-sen University, Kaohsiung, Taiwan. Electronic address:
Background: Obesity and circadian rhythm disruption are significant global health concerns, contributing to an increased risk of metabolic disorders. Both adipose tissue and circadian rhythms play critical roles in maintaining energy homeostasis, and their dysfunction is closely linked to obesity. This study aimed to assess the effects of chronic low-dose SR9009, a REV-ERB ligand, on circadian disruption induced by constant light exposure in mice.
View Article and Find Full Text PDFDT-13 Mediates Ligand-Dependent Activation of PPARγ Response Elements In Vitro.
Biology (Basel)
December 2024
Charité-Universitätsmedizin Berlin, Corporate Member of Freie Universität Berlin and Humboldt-Universität zu Berlin, Institute of Diagnostic Laboratory Medicine, Clinical Chemistry and Pathobiochemistry, Augustenburger Platz 1, D-13353 Berlin, Germany.
Activation of inflammatory pathways releases a storm of cytokines. Moreover, unregulated cytokines contribute to chronic inflammatory disorders. However, ligand-activated peroxisome proliferator-activated receptor gamma (PPARγ) is involved in suppressing inflammatory cytokines via transrepression of nuclear factor kappa B (NFκB).
View Article and Find Full Text PDFWant AI Summaries of new PubMed Abstracts delivered to your In-box?
Enter search terms and have AI summaries delivered each week - change queries or unsubscribe any time!