Characteristics of the peroxisome proliferator activated receptor γ (PPARγ) ligand induced apoptosis in colon cancer cells. Issue 5 (1st May 2002)

• Record Type: Journal Article
• Authors: Shimada, T; Kojima, K; Yoshiura, K; Hiraishi, H; Terano, A
• Is Part Of: Gut. Volume 50:Issue 5(2002)
• Page Start: 658
• Page End: 664
• Publication Date: 2002-05-01
• Subjects: peroxisome proliferator activated receptor -- apoptosis -- colon cancer; PPAR, peroxisome proliferator activated receptor -- RT-PCR, reverse transcription-polymerase chain reaction -- 15d-PGJ2, 15-deoxy-δ12, 14- prostaglandin J2 -- TGZ, troglitazone -- APC, adenomatous polyposis coli -- RXR, retinoid X receptor -- cPGI, carbaprostacyclin -- AT-RA, all-trans retinoic acid -- 9c-RA, 9-cis-retinoic acid -- FBS, fetal bovine serum -- CHX, cycloheximide -- RAR, retinoid A receptor -- COX-2, cyclooxygenase 2 -- PI3-kinase, phosphatidylinositol 3-kinase -- Tcf/Lef, T cell factor/lymphoid enhancer factor -- PBS, phosphate buffered saline -- BrdU, bromodeoxyuridine -- MAP, mitogen activated protein; Gastroenterology -- Periodicals; 616.33
• DOI: 10.1136/gut.50.5.658
• Languages: English
• ISSNs: 0017-5749

Abstract

Abstract : Background: Involvement of peroxisome proliferator activated receptor γ (PPARγ) in the growth response of colon cancer cells has been suggested. Aims: To investigate the characteristics of PPARγ induced apoptosis in colon cancer cells. Methods: The effects of ligands for each of the PPAR subtypes (α, δ, and γ) on DNA synthesis and cell viability were examined in HT-29 colon cancer cells. Modulation of apoptosis related gene expression by PPARγ ligands was screened with cDNA arrays, and the results were confirmed by quantitative reverse transcription-polymerase chain reaction (RT-PCR) analysis. Results: PPARα, PPARδ, and PPARγ were all expressed in HT-29 cells. PPARγ ligands, 15-deoxy-δ 12, 14 -prostaglandin J2 (15d-PGJ2 ) and troglitazone (TGZ), suppressed DNA synthesis of HT-29 cells whereas ligands for PPARα and PPARδ had no significant effects. Both 15d-PGJ2 and TGZ induced HT-29 cell death in a dose dependent manner which was associated with an increase in fragmented DNA and was sensitive to a caspase inhibitor. Among several genes selected by cDNA array screening, quantitative RT-PCR analysis confirmed downregulation of c-myc expression and upregulation of c-jun and gadd153 expression by 15d-PGJ2 and TGZ. PPARγ induced apoptosis was antagonised by the presence of serum in the culture medium, and interaction between PPARγ signalling and cell survival signalling through the phosphatidylinositol 3-kinase pathway was suggested. Conclusions: As c-myc is an important target gene of the adenomatous polyposis coli (APC)/β-catenin and/or APC/γ-catenin pathway, activation of PPARγ signalling appears to compensate for deregulated c-myc expression caused by mutated APC. The present results suggest the potential usefulness of PPARγ ligands for chemoprevention and treatment of colon cancers.