Therapeutic Molecular Targetingof 15-Lipoxygenase-1 in Colon Cancer

Wu, Yuanqing; Fang, Bingliang; Xiao, Yang; Wang, Li; Chen, Dongning; Krasnykh, Victor; Carter, Bing Z.; Morris, Jeffrey S.; Shureiqi, Imad

doi:10.1038/mt.2008.44

Cited by 31 publications

(39 citation statements)

References 42 publications

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“…15-LOX-2 was undetected in both adenomas and normal tissue [36] . Apart from this, in vivo studies from Nixon et al [24] and Wu et al [26] , and evidence of transcriptional silencing of 15-LOX-1 in cancer cells in a different study [35] strengthened the anti-carcinogenic role of 15-LOX-1. Yuri et al [38] have reported down-regulation of 15-LOX-1 in colorectal adenomas.…”

Section: Anti-carcinogenic Roles Of 15-lox-1 In Colon Cancermentioning

confidence: 95%

“…Although several inter-conflicting reports have been published, convincing recent evidences from several in vitro and in vivo studies, especially the ones in the latter category from Nixon et al [24] , Shureiqi et al [25] and Wu et al [26] ( fig. 2 ), makes us believe that the overall effect of 15-LOX-1 and its 13-S-HODE metabolite is largely anti-carcinogenic in colorectal cancer.…”

Section: Is 15-lox-1 Pro-or Anti-carcinogenic? Weighing the Evidencesmentioning

confidence: 95%

“…Most of the data in the field of 15-LOX-1 and cancer have been generated from in vitro models. In contrast, mechanistic in vivo studies [24][25][26] are rare in this field. Probably, this can be explained by the fact that mice do not express 15-LOX-1.…”

Section: Anti-carcinogenic Roles Of 15-lox-1 In Colon Cancermentioning

confidence: 99%

“…A specific COX-2 inhibitor, SC-236, was found to induce apoptosis in gastric cancer cells, possibly through up-regulation of 15-LOX-1 and 13-S-HODE [55] . Specific molecular targeting of the 15-LOX-1 gene to increase its expression in colon cancer cells and eventually inhibiting colonic tumorigenesis, both in vitro and in model systems in vivo, has been demonstrated by Wu et al [26] . This last publication has provided scopes for further research in this field of specific molecular targeting to enhance gene expression in cancer chemotherapeutics.…”

Section: Therapeutic Targeting Of Fatty Acid Metabolism In Colon Cancermentioning

confidence: 99%

“…Some animal studies have been undertaken and have provided useful insights into LOX biology [24][25][26] . However, functional transgenic and knockout mouse studies of 15-LOX-1 in colorectal carcinogenesis are lacking.…”

Section: Scope For Future Developments/use Of Animal Modelsmentioning

confidence: 99%

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15-Lipoxygenase-1 in Colorectal Cancer: A Review

Bhattacharya¹,

Mathew²,

Jayne³

et al. 2009

Tumor Biol

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Objective: Enzymes involved in the oxidative metabolism of n-6 polyunsaturated fatty acids, like lipoxygenase (LOX) and cyclooxygenase (COX), are significant in the pathogenesis of colorectal cancer. Of these enzymes, 15-LOX-1 is expressed in colon. Aim of this article is to describe the role and regulation of 15-LOX-1 in colorectal cancer and highlight its importance in cancer therapeutics. Methods: For our electronic literature research in PubMed and MEDLINE, key words related to 15-LOX-1 and colorectal cancer were used to find articles for this review. Results: From the evidences, we believe that 15-LOX-1 has anti-carcinogenic effects in colorectal cancer, dependent or independent of its metabolites, and is manifested through downstream pathways involving cGMP, PPAR, p53, p21 and NAG-1, increasing apoptosis and decreasing proliferation in cancer cells. Regulation of 15-LOX-1 expression is achieved at transcription level by global histone acetylation and may also be dependent on GATA-6, IL-4 and IL-13. Positive relationship exists between 15-LOX-1 and survival in colorectal cancer. Conclusion: Evidences strongly support that therapeutic modulation of 15-LOX-1 may be a key to the treatment of colorectal cancer. However, it is still undecided whether the up-regulation of 15-LOX-1 alone can be sufficient to treat colorectal cancer and further studies are awaited.

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Section: Anti-carcinogenic Roles Of 15-lox-1 In Colon Cancermentioning

confidence: 95%

Section: Is 15-lox-1 Pro-or Anti-carcinogenic? Weighing the Evidencesmentioning

confidence: 95%

Section: Anti-carcinogenic Roles Of 15-lox-1 In Colon Cancermentioning

confidence: 99%

Section: Therapeutic Targeting Of Fatty Acid Metabolism In Colon Cancermentioning

confidence: 99%

Section: Scope For Future Developments/use Of Animal Modelsmentioning

confidence: 99%

See 3 more Smart Citations

15-Lipoxygenase-1 in Colorectal Cancer: A Review

Bhattacharya¹,

Mathew²,

Jayne³

et al. 2009

Tumor Biol

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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 as a tumor suppressor gene in colon cancer: is the verdict in?

Lee

Zuo

Shureiqi

2011

Cancer Metastasis Rev

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15-Lipoxygenase-1 (15-LOX-1) is an inducible and highly regulated enzyme in normal human cells that plays a key role in the production of lipid signaling mediators, such as 13-hydroxyoctadecadienoic acid (13-HODE) from linoleic acid. 15-LOX-1 significantly contributes to resolution of inflammation and to terminal differentiation of normal cells. 15-LOX-1 is downregulated in human colorectal polyps and cancers. Emerging data support a tumor suppressor role for 15-LOX-1, especially in colon cancer. These data indicate that 15-LOX-1 promotes various antitumorigenic events, including cell differentiation and apoptosis, and inhibits chronic inflammation, angiogenesis, and metastasis. The transcriptional repression of 15-LOX-1 in colon cancer cells is complex and involves multiple mechanisms (e.g., histone methylation, transcriptional repressor binding). Re-expression of 15-LOX-1 in colon cancer cells can function as an important therapeutic mechanism and could be further exploited to develop novel treatment approaches for this common cancer.

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Therapeutic Molecular Targetingof 15-Lipoxygenase-1 in Colon Cancer

Cited by 31 publications

References 42 publications

15-Lipoxygenase-1 in Colorectal Cancer: A Review

15-Lipoxygenase-1 in Colorectal Cancer: A Review

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

15-Lipoxygenase-1 as a tumor suppressor gene in colon cancer: is the verdict in?

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