Journal Article

Activation of the PPAR pathway induces apoptosis and COX-2 inhibition in HT-29 human colon cancer cells

Wan-Lin Yang and Harold Frucht

in Carcinogenesis

Volume 22, issue 9, pages 1379-1383
Published in print September 2001 | ISSN: 0143-3334
Published online September 2001 | e-ISSN: 1460-2180 | DOI: http://dx.doi.org/10.1093/carcin/22.9.1379
Activation of the PPAR pathway induces apoptosis and COX-2 inhibition in HT-29 human colon cancer cells

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The γ isoform of the peroxisome proliferator-activated receptor (PPARγ) is a nuclear receptor that regulates adipocyte differentiation. Recently it has been shown to be expressed in human colonic mucosa and cancer, but its role in colon carcinogenesis and progression is still unclear. We demonstrate that activation of PPARγ by ciglitazone (cig), a selective PPARγ ligand, induces HT-29 human colon cancer cells to undergo apoptosis. Treatment with cig also down-regulates expression of cyclooxygenase-2 (COX-2) protein. Simultaneous exposure of cells to cig and 9-cis-retinoic acid (9-cis-RA), a ligand for retinoid X receptor, results in an increased apoptotic effect and increased inhibition of COX-2 expression, compared with cells treated with either cig or 9-cis-RA alone. As COX-2 is overexpressed in human colon cancer and has been implicated in augmenting invasiveness and tumorigenecity, the ability of PPARγ activation to decrease COX-2 expression and induce apoptosis suggests that the PPARγ pathway may be considered as a therapeutic target for colon cancer.

Keywords: APC, adenomatous polyposis coli; cig, ciglitazone; 9-cis-RA, 9-cis-retinoic acid; COX, cyclooxygenase; FBS, fetal bovine serum; NSAIDs, non-steroidal anti-inflammatory drugs; PG, prostaglandin; PPRE, peroxisome proliferator response elements; PPAR, peroxisome proliferator-activated receptor; RXR, retinoid X receptor.

Journal Article.  3909 words.  Illustrated.

Subjects: Clinical Cytogenetics and Molecular Genetics

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