The retinoid fenretinide inhibits proliferation and downregulates cyclooxygenase-2 gene expression in human colon adenocarcinoma cell lines

Greogory Merritt, Elias T. Aliprandis, Francesco Prada, Basil Rigas, Khosrow Kashfi

Research output: Contribution to journalArticlepeer-review

Abstract

Fenretinide [N-(4-Hydroxyphenyl)retinamide, 4-HPR] (10-10-10-6 M) treatment of HT-29 human colon cancer cells for 24-72 h significantly inhibited their growth. Using HCT-15 cells, 4-HPR had limited inhibitory effects on cell proliferation over the same concentration range and time period. The inhibitory effects of 4-HPR on cell growth in HT-29 cells were markedly reduced in the presence of exogenously added prostaglandins (PGs), suggesting a possible role for inhibition of PG synthesis as a mechanism for 4-HPR's antiproliferative effects. Inhibition of PGE2 production was caused by 4-HPR in a concentration-dependent manner and decreased COX-2 but not COX-1 mRNA levels; this is the first indication that 4-HPR selectively inhibits COX-2 gene expression. Our findings suggest a possible mechanism for the chemopreventive and anti-proliferative effects of 4-HPR.

Original languageEnglish
Pages (from-to)15-23
Number of pages9
JournalCancer Letters
Volume164
Issue number1
DOIs
Publication statusPublished - Mar 10 2001

Keywords

  • Colon cancer
  • Cyclooxygenase
  • Fenretinide
  • Prostaglandins
  • Retinoids

ASJC Scopus subject areas

  • Cancer Research
  • Molecular Biology
  • Oncology

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