15-Lipoxygenase-1 has anti-tumorigenic effects in colorectal cancer

Nixon, Jennifer B.; Kim, Kyung Soo; Lamb, Patricia W.; Bottone, Frank G.; Eling, Thomas E.

doi:10.1016/j.plefa.2003.06.001

Cited by 71 publications

(68 citation statements)

References 27 publications

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“…Thus, a dichotomy exists between the expression of 15-LOX-1 in colorectal cells and its biological function. The higher expression in tumors, as measured by Western analysis, would seem to suggest a protumorigenic activity; however, overexpression of 15-LOX-1 in xenograft tumors reduces growth, indicating an antitumorigenic activity (10). Further experiments are necessary to resolve these issues, but our working hypothesis is that expression of 15-LOX-1 exerts an antitumorigenic effect in the colon but is protumorigenic in the prostate.…”

Section: (S)-hydroxyoctadecadienoic Acid [13(s)-hode] and 15(s)-hydmentioning

confidence: 93%

“…In the normal colon, expression is highly localized to the mucosal epithelium (10), whereas tumors may express 15-LOX-1 in both the neoplastic epithelium and the infiltrating inflammatory cells (11,12). Neoplastic colonic epithelium treated in vitro with the short-chain fatty acid sodium butyrate can be induced to differentiate and undergo apoptosis associated with up-regulation of 15-LOX-1 (4).…”

Section: (S)-hydroxyoctadecadienoic Acid [13(s)-hode] and 15(s)-hydmentioning

confidence: 99%

“…Shureiqi et al used immunohistochemistry to show greater expression of 15-LOX-1 in normal human colorectal tissues compared with tumors, whereas infiltrating inflammatory cells expressed the enzyme (11). In contrast, Western blot analysis indicates that the tumor mass contains higher levels of 15-LOX-1 than normal tissues perhaps due to the contribution of inflammatory cells (10). Thus, a dichotomy exists between the expression of 15-LOX-1 in colorectal cells and its biological function.…”

Section: (S)-hydroxyoctadecadienoic Acid [13(s)-hode] and 15(s)-hydmentioning

confidence: 99%

“…Previously, we constructed HCT-116 human colorectal cells that ectopically express 15-LOX-1 and reported that these cells exhibited a reduced tumor formation in the nude mouse xenograft model (10) To decipher the molecular mechanisms responsible for reduced growth and reduction in tumor volume by the 15-LOX-1-overexpressing cells, we decided to determine if the expression of 15-LOX-1 altered the expression of genes related to control of cell proliferation. We selected two different membrane-based microarray systems to measure changes in gene expression, one that examines human cell cycle genes and a second that measures human p53 signaling pathway genes.…”

Section: Overexpression Of 15-lox-1 In Hct-116 Cells Reduces Cell Growthmentioning

confidence: 99%

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Overexpression of 15-Lipoxygenase-1 Induces Growth Arrest through Phosphorylation of p53 in Human Colorectal Cancer Cells

Kim

Baek

Bottone

et al. 2005

Molecular Cancer Research

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To investigate the function of 15-lipoxygenase-1 (15-LOX-1) in human colorectal cancer, we overexpressed 15-LOX-1 in inhibitor PD146176 did not inhibit the phosphorylation of p53 at Ser 15 in 15-LOX-1-overexpressing cells. Nonetheless, the growth-inhibitory effects of 15-LOX-1 were p53 dependent, as 15-LOX-1 overexpression had no effect on cell growth in p53 (À/À) HCT-116 cells. Finally, treatment of HCT-116-15-LOX-1 cells with different kinase inhibitors suggested that the effects of 15-LOX-1 on p53 phosphorylation and activation were due to effects on DNA-dependent protein kinase. Collectively, these findings suggest a new mechanism to explain the biological activity of 15-LOX-1, where 15-LOX plays a stoichiometric role in activating a DNA-dependent protein kinase -dependent pathway that leads to p53-dependent growth arrest. (Mol Cancer Res 2005;3(9):511 -7)

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Section: (S)-hydroxyoctadecadienoic Acid [13(s)-hode] and 15(s)-hydmentioning

confidence: 93%

Section: (S)-hydroxyoctadecadienoic Acid [13(s)-hode] and 15(s)-hydmentioning

confidence: 99%

Section: (S)-hydroxyoctadecadienoic Acid [13(s)-hode] and 15(s)-hydmentioning

confidence: 99%

Section: Overexpression Of 15-lox-1 In Hct-116 Cells Reduces Cell Growthmentioning

confidence: 99%

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Overexpression of 15-Lipoxygenase-1 Induces Growth Arrest through Phosphorylation of p53 in Human Colorectal Cancer Cells

Kim

Baek

Bottone

et al. 2005

Molecular Cancer Research

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“…Given that 5-LOX [14], 12-LOX [13] and 15-LOX [37] are expressed by intestinal epithelial cells and that there is differentiated expression of these enzymes during epithelial cell differentiation, these eicosanoids may also have an important role in the physiology of the epithelium. Thus, Kamitani et al [13] suggested that 12-LOX, and/or the lipid products synthesized by this enzyme are involved in intestinal epithelial cell differentiation and apoptosis.…”

Section: Role Of Eicosanoids In the Control Of Intestinal Epithelial mentioning

confidence: 99%

Role of eicosanoids on intestinal epithelial homeostasis

Ferrer

Moreno

2010

Biochemical Pharmacology

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The intestinal epithelium is a highly dynamic system that is continuously renewed by a process involving cell proliferation and differentiation. Moreover, it is the main interface with the external environment, and maintenance and regulation of the epithelial structure and epithelial barrier function are key determinants of digestive health and host well-being. The tight junction, a multiprotein complex composed of transmembrane proteins associated with the cytoskeletal peri-junctional ring of actin and myosin, is an essential component of this barrier that is strictly regulated in a spatio-temporal manner by a complex signaling network. Defects in the intestinal epithelial barrier function have been observed in inflammatory bowel disease, and a classic example of the connection between inflammation and cancer is the increased risk of colorectal cancer in patients with inflammatory bowel disease. In recent years, several molecules have emerged as critical players contributing to inflammationassociated colorectal cancer. For example, eicosanoids derived from arachidonic acid are proposed as mediators involved in the regulation of epithelial structure/function. Interestingly, the tissue concentration of eicosanoids increases during mucosal inflammation and colorectal cancer development. This overview focuses on the physiological and physiopathological roles of eicosanoids in cell growth/cell differentiation/apoptosis and in the paracellular permeability of the intestinal epithelium. A better understanding of these processes will foster new ideas for the development of therapies for these chronic disorders.

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15‐LOX‐1 suppression of hypoxia‐induced metastatic phenotype and HIF‐1α expression in human colon cancer cells

Mao

Zuo

et al. 2014

Cancer Medicine

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The expression of 15-lipoxygenase-1 (15-LOX-1) is downregulated in colon cancer and other major cancers, and 15-LOX-1 reexpression in cancer cells suppresses colonic tumorigenesis. Various lines of evidence indicate that 15-LOX-1 expression suppresses premetastatic stages of colonic tumorigenesis; nevertheless, the role of 15-LOX-1 loss of expression in cancer epithelial cells in metastases continues to be debated. Hypoxia, a common feature of the cancer microenvironment, promotes prometastatic mechanisms such as the upregulation of hypoxia-inducible factor (HIF)-1α, a transcriptional master regulator that enhances cancer cell metastatic potential, angiogenesis, and tumor cell invasion and migration. We have, therefore, tested whether restoring 15-LOX-1 in colon cancer cells affects cancer cells' hypoxia response that promotes metastasis. We found that 15-LOX-1 reexpression in HCT116, HT29LMM, and LoVo colon cancer cells inhibited survival, vascular endothelial growth factor (VEGF) expression, angiogenesis, cancer cell migration and invasion, and HIF-1α protein expression and stability under hypoxia. These findings demonstrate that 15-LOX-1 expression loss in cancer cells promotes metastasis and that therapeutically targeting ubiquitous 15-LOX-1 loss in cancer cells has the potential to suppress metastasis.

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15-Lipoxygenase-1 has anti-tumorigenic effects in colorectal cancer

Cited by 71 publications

References 27 publications

Overexpression of 15-Lipoxygenase-1 Induces Growth Arrest through Phosphorylation of p53 in Human Colorectal Cancer Cells

Overexpression of 15-Lipoxygenase-1 Induces Growth Arrest through Phosphorylation of p53 in Human Colorectal Cancer Cells

Role of eicosanoids on intestinal epithelial homeostasis

15‐LOX‐1 suppression of hypoxia‐induced metastatic phenotype and HIF‐1α expression in human colon cancer cells

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