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 language | English (US) |
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Pages (from-to) | 111-122 |
Number of pages | 12 |
Journal | Prostaglandins and Other Lipid Mediators |
Volume | 73 |
Issue number | 1-2 |
DOIs | |
State | Published - Jan 2004 |
Externally published | Yes |
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