15-LOX-1 inhibits p21 (Cip/WAF 1) expression by enhancing MEK-ERK1/2 signaling in colon carcinoma cells

Masahiro Yoshinaga, F. Gregory Buchanan, Raymond N. DuBois

    Research output: Contribution to journalArticlepeer-review

    27 Scopus citations

    Abstract

    Currently, some controversy exists regarding the precise role of 15-lipoxygenase-1 (15-LOX-1) in colorectal carcinogenesis and other aspects of cancer biology. The aim of this study was to evaluate the effect of 15-LOX-1 on p21 (Cip/WAF 1) expression and growth regulation in human colon carcinoma cells. The effect of 13-S-hydroxyoctadecadienoic acid (HODE), a product of 15-LOX-1, on p21 (Cip/WAF 1) expression was evaluated in Caco-2 cells treated with sodium butyrate (NaBT) and/or nordihydroguaiarectic acid (NDGA), a LOX inhibitor. The effect of transfecting HCT-116 cells with 15-LOX-1 was also examined. NaBT-induced p21 (Cip/WAF 1) expression was enhanced by treatment with NDGA and 13-S-HODE reversed NaBT-induced p21 (Cip/WAF 1) expression in Caco-2 cells. Overexpression of 15-LOX-1 induced extracellular signal-related kinase (ERK) 1/ 2 phosphorylation, decreased p21 (Cip/WAF 1) expression, and increased HCT-116 cell growth. Treatment with NDGA decreased ERK 1/2 phosphorylation, and increased p21 (Cip/WAF 1) expression in 15-LOX-1 overexpressing HCT-116 cells. Our experimental results support the hypothesis that 15-LOX-1 may have "pro-neoplastic" effects during the development of colorectal cancer.

    Original languageEnglish (US)
    Pages (from-to)111-122
    Number of pages12
    JournalProstaglandins and Other Lipid Mediators
    Volume73
    Issue number1-2
    DOIs
    StatePublished - Jan 2004

    Keywords

    • 13-S-HODE
    • 13-S-hydroxyoctadecadienoic acid
    • 15-LOX-1
    • 15-lipoxygenase-1
    • ERK
    • Extracellular signal-related kinase
    • NDGA
    • NaBT
    • Nordihydroguaiarectic acid
    • PPAR gamma
    • Peroxisome proliferator-activated receptor gamma
    • Sodium butyrate
    • p21 (Cip/WAF 1)

    ASJC Scopus subject areas

    • Biochemistry
    • Physiology
    • Pharmacology
    • Cell Biology

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