Vascular endothelial growth factor production in human prostate cancer cells is stimulated by overexpression of platelet 12-lipoxygenase

McCabe, N. Patrick; Selman, Steven H.; Jankun, Jerzy

doi:10.1002/pros.20360

Cited by 31 publications

(16 citation statements)

References 40 publications

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“…In prostate cancer cells, this has been reported by two independent groups [38,83]. Both NDGA and baicalein reduced VEGF expression, confirming that the enzymatic activity of 12-LOX plays a significant role in the regulation of VEGF gene expression.…”

Section: Regulation Of Tumor Cell Death By Loxsupporting

confidence: 64%

Lipoxygenase metabolism: roles in tumor progression and survival

Pidgeon

Lysaght

Krishnamoorthy

et al. 2007

Cancer Metastasis Rev

269

206

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The metabolism of arachidonic acid through lipoxygenase pathways leads to the generation of various biologically active eicosanoids. The expression of these enzymes vary throughout the progression of various cancers, and thereby they have been shown to regulate aspects of tumor development. Substantial evidence supports a functional role for lipoxygenase-catalyzed arachidonic and linoleic acid metabolism in cancer development. Pharmacologic and natural inhibitors of lipoxygenases have been shown to suppress carcinogenesis and tumor growth in a number of experimental models. Signaling of hydro[peroxy]fatty acids following arachidonic or linoleic acid metabolism potentially effect diverse biological phenomenon regulating processes such as cell growth, cell survival, angiogenesis, cell invasion, metastatic potential and immunomodulation. However, the effects of distinct LOX isoforms differ considerably with respect to their effects on both the individual mechanisms described and the tumor being examined. 5-LOX and platelet type 12-LOX are generally considered pro-carcinogenic, with the role of 15-LOX-1 remaining controversial, while 15-LOX-2 suppresses carcinogenesis. In this review, we focus on the molecular mechanisms regulated by LOX metabolism in some of the major cancers. We discuss the effects of LOXs on tumor cell proliferation, their roles in cell cycle control and cell death induction, effects on angiogenesis, migration and the immune response, as well as the signal transduction pathways involved in these processes. Understanding the molecular mechanisms underlying the anti-tumor effect of specific, or general, LOX inhibitors may lead to the design of biologically and pharmacologically targeted therapeutic strategies inhibiting LOX isoforms and/or their biologically active metabolites, that may ultimately prove useful in the treatment of cancer, either alone or in combination with conventional therapies.

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Section: Regulation Of Tumor Cell Death By Loxsupporting

confidence: 64%

Lipoxygenase metabolism: roles in tumor progression and survival

Pidgeon

Lysaght

Krishnamoorthy

et al. 2007

Cancer Metastasis Rev

269

206

View full text Add to dashboard Cite

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“…12S-HETE also increased the release of another proangiogenic molecule, VEGF, from prostate tumor cells, whereas 12-LO inhibitors had the opposite effect, suggesting that 12S-HETE is an endogenous regulator of VEGF secretion by these cells [153]. Overexpression of 12-LO had a similar effect [141,153]. …”

Section: Biological Actions Of Hetes and Oxoetesmentioning

confidence: 99%

Biosynthesis, biological effects, and receptors of hydroxyeicosatetraenoic acids (HETEs) and oxoeicosatetraenoic acids (oxo-ETEs) derived from arachidonic acid

Powell

Rokach

2015

Biochimica et Biophysica Acta (BBA) - Molecular and Cell Biolog

263

206

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Arachidonic acid can be oxygenated by a variety of different enzymes, including lipoxygenases, cyclooxygenases, and cytochrome P450s, and can be converted to a complex mixture of oxygenated products as a result of lipid peroxidation. The initial products in these reactions are hydroperoxyeicosatetraenoic acids (HpETEs) and hydroxyeicosatetraenoic acids (HETEs). Oxoeicosatetraenoic acids (oxo-ETEs) can be formed by the actions of various dehydrogenases on HETEs or by dehydration of HpETEs. Although a large number of different HETEs and oxo-ETEs have been identified, this review will focus principally on 5-oxo-ETE, 5S-HETE, 12S-HETE, and 15S-HETE. Other related arachidonic acid metabolites will also be discussed in less detail. 5-Oxo-ETE is synthesized by oxidation of the 5-lipoxygenase product 5S-HETE by the selective enzyme, 5-hydroxyeicosanoid dehydrogenase. It actions are mediated by the selective OXE receptor, which is highly expressed on eosinophils, suggesting that it may be important in eosinophilic diseases such as asthma. 5-Oxo-ETE also appears to stimulate tumor cell proliferation and may also be involved in cancer. Highly selective and potent OXE receptor antagonists have recently become available and could help to clarify its pathophysiological role. The 12-lipoxygenase product 12S-HETE acts by the GPR31 receptor and promotes tumor cell proliferation and metastasis and could therefore be a promising target in cancer therapy. It may also be involved as a proinflammatory mediator in diabetes. In contrast, 15S-HETE may have a protective effect in cancer. In addition to GPCRs, higher concentration of HETEs and oxo-ETEs can activate peroxisome proliferator-activated receptors (PPARs) and could potentially regulate a variety of processes by this mechanism.

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“…Studies of tumor xenografts in mice, demonstrated that prostate tumors generated from 12-LOX overexpressing prostate cancer PC-3 cells were of a highly angiogenic phenotype [9]. This phenomenon was later attributed to the enhanced secretion of VEGF induced by 12-LOX in prostate cancer cells [8, 12]. …”

Section: Introductionmentioning

confidence: 99%

12-Lipoxygenase and the regulation of hypoxia-inducible factor in prostate cancer cells

Krishnamoorthy

Jin

Cai

et al. 2010

Experimental Cell Research

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Abstract12-lipoxygenase, an arachidonic acid metabolizing enzyme of the lipoxygenase pathway, has been implicated as a major factor in promoting prostate cancer progression and metastasis. The ability of 12-LOX to aggravate the disease was linked to its proangiogenic role. Recent studies clearly demonstrated that 12-LOX enhances the expression and secretion of the angiogenic factor, vascular endothelial growth factor (VEGF) thus providing a direct link between this enzyme and its angiogenic properties. In the present study we have investigated the relationship between 12-LOX and hypoxia inducible factor-1α (HIF-1α), a transcription factor involved in the regulation of VEGF expression under hypoxic conditions in solid tumors. Our findings have revealed that HIF-1 is one of the target transcription factors regulated by 12-LOX and 12(S)-HETE, in hypoxic tumor cells of the prostate. Regulation of HIF-1α by 12-LOX adds to the complexity of pathways mediated by this enzyme in promoting prostate cancer angiogenesis and metastasis. We have evidence that 12-LOX increases the protein level, mRNA, and functional activity of HIF-1α under hypoxic conditions, one of the mechanisms by which it upregulates VEGF secretion and activity.

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Vascular endothelial growth factor production in human prostate cancer cells is stimulated by overexpression of platelet 12-lipoxygenase

Abstract: Our data provide insight into a possible mechanism by which prostate cancer cells with elevated expression of P12-LOX stimulate VEGF production, thus increasing their angiogenic potential.

Cited by 31 publications

References 40 publications

Lipoxygenase metabolism: roles in tumor progression and survival

Lipoxygenase metabolism: roles in tumor progression and survival

Biosynthesis, biological effects, and receptors of hydroxyeicosatetraenoic acids (HETEs) and oxoeicosatetraenoic acids (oxo-ETEs) derived from arachidonic acid

12-Lipoxygenase and the regulation of hypoxia-inducible factor in prostate cancer cells

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