Arachidonic Acid Stimulates Prostate Cancer Cell Growth: Critical Role of 5-Lipoxygenase

Ghosh, J. J.; Myers, Charles E.

doi:10.1006/bbrc.1997.6799

Cited by 230 publications

(161 citation statements)

References 26 publications

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“…11 Arachidonic acid stimulated PC-3 cell growth, which was inhibited by selective 5-LOX inhibitors but not by 12-LOX or cyclooxygenase inhibitors. Furthermore, 5-HETE was produced from exogenous AA in PC-3 cells.…”

Section: Discussionmentioning

confidence: 93%

“…These include the arachidonate 5-lipoxygenase, 11 12-lipoxygenase, 10 and reticulocyte type of 15-lipoxygenase (15-LOX-1). 12 In this study we have used assays of enzyme activity and immunohistochemistry to document expression of the recently described 15-lipoxygenase enzyme 15-LOX-2 8 in benign human prostate epithelium and its reduction in prostate adenocarcinoma.…”

Section: Discussionmentioning

confidence: 99%

“…Furthermore, 5-HETE was produced from exogenous AA in PC-3 cells. 11 More recently, these investigators and others have demonstrated induction of apoptosis in PC-3 and LNCaP cell lines by inhibitors of 5-LOX and 5-LOX-activating protein (FLAP). 25,26 Again, we did not observe 5-HETE production from exogenous AA in benign prostate or a limited number of fresh-frozen prostate tumors.…”

Section: Discussionmentioning

confidence: 99%

“…In continuing efforts to elucidate potentially important molecular alterations in prostate cancer development or progression, a limited number of recent investigations using both human tissues and prostate carcinoma cell lines have begun focusing on AA-metabolizing enzymes, including cyclooxygenase, 9 12-LOX, 10 5-LOX, 11 and 15-LOX-1. 12 In the current study, we have characterized the expression of 15-LOX-2 in benign prostate by immunohistochemistry, demonstrated the ability of benign prostate to form the enzymatic product of 15-LOX-2 (15-HETE) from AA, and begun exploring the possible altered expression of 15-LOX-2 and 15-HETE formation in prostate adenocarcinoma.…”

mentioning

confidence: 99%

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15-Lipoxygenase-2 (15-LOX-2) Is Expressed in Benign Prostatic Epithelium and Reduced in Prostate Adenocarcinoma

Shappell

Boeglin

Olson

et al. 1999

The American Journal of Pathology

141

120

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Human 15S-lipoxygenase-2 (15-LOX-2) is a recently identified lipoxygenase that has approximately 40% sequence identity to the known human 5S-, 12S-, and 15S-lipoxygenases. 15-LOX-2 has a limited tissue dis-Arachidonic acid (AA) metabolites are important mediators of a variety of physiological processes and inflammatory reactions. In addition, alterations in AA metabolism may potentially mediate key steps in certain neoplastic processes. 1-3 AA is metabolized via cyclooxygenase to prostaglandins, prostacyclin, and thromboxane, 4 and via lipoxygenases (LOX) to hydroxyeicosatetraenoic acids (HETEs) or leukotrienes (5-LOX pathway). 5,6 Until recently, three lipoxygenases were recognized in humans: a 5S-LOX found in leukocytes, a 12S-LOX found in platelets and certain epithelia, and a 15S-LOX in reticulocytes, eosinophils, macrophages, and skin. 7 Recently, in studying lipoxygenase expression in human skin, Brash et al 8 discovered a second 15S-lipoxygenase (herein referred to as 15-LOX-2). The cDNA-derived amino acid sequence of 15-LOX-2 showed only 44% identity to 5-LOX and 38% to 39% identity to 12-LOX and the reticulocyte type of 15-LOX

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Section: Discussionmentioning

confidence: 93%

Section: Discussionmentioning

confidence: 99%

Section: Discussionmentioning

confidence: 99%

mentioning

confidence: 99%

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15-Lipoxygenase-2 (15-LOX-2) Is Expressed in Benign Prostatic Epithelium and Reduced in Prostate Adenocarcinoma

Shappell

Boeglin

Olson

et al. 1999

The American Journal of Pathology

141

120

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“…Unlike prostaglandins, which are short-lived and synthesized only according to immediate need and then rapidly degraded, LTs are quite stable, with a half-life approaching 4 hours (9). LTs have been reported to play a prominent inductive role in the progression of a variety of cancers, with 5-LOX found to be expressed in lung, colon, breast, prostate, pancreatic, and other cancers (13)(14)(15)(16)(17)(18)(19). Recent studies have also demonstrated expression of the 5-LOX pathway enzyme LTA 4 hydrolase in esophageal cancers (20).…”

Section: Introductionmentioning

confidence: 99%

Modulation of Pulmonary Leukotriene B4 Production by Cyclooxygenase-2 Inhibitors and Lipopolysaccharide

Mao

Tsu

Dubinett

et al. 2004

Clinical Cancer Research

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Purpose: Emerging data continue to link carcinogenesis to inflammatory events involving the eicosanoid metabolic pathways. We therefore evaluated the effects of cyclooxygenase (COX)-2 inhibition on leukotriene (LT) B 4 synthesis in the lungs of active smokers, as part of a pilot lung cancer chemoprevention study with celecoxib (Celebrex), an oral COX-2 inhibitor.Experimental Design: Bronchoalveolar lavage was performed before celecoxib treatment and after 1 month of celecoxib treatment to recover alveolar macrophages (AMs) and lining fluid for study. After harvest, AMs were immediately stimulated in vitro with the calcium ionophore A23187. AMs obtained from smokers before treatment and from ex-smoker control subjects were also cultured overnight with SC58236, a selective COX-2 inhibitor, with or without lipopolysaccharide stimulation.Results: Treatment with oral celecoxib only modestly increased LTB 4 levels in bronchoalveolar lavage, without increasing the mRNA transcription of 5-lipoxygenase (5-LOX) or 5-LOX-activating protein in AMs, whereas the acute calcium ionophore-stimulated LTB 4 production from smokers' AMs was markedly increased by 10.6-fold. In addition, smokers' AMs were twice as responsive in producing LTB 4 when exposed to lipopolysaccharide compared with ex-smokers' AMs. Concomitant COX-2 inhibition with SC58236, however, did not significantly impact these changes, whereas the 5-LOX inhibitor Zileuton blocked the generation of LTB 4 in a dose-responsive manner. Finally, cycloheximide increased the production of LTB 4 under all conditions, suggesting a shunting phenomenon and/or the presence of pathway inhibitors.Conclusions: Our findings suggest that whereas oral celecoxib is capable of modulating LTB 4 production in the lung microenvironment, under physiologic conditions, this effect is probably not functionally significant.

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5-lipoxygenase inhibitors reduce PC-3 cell proliferation and initiate nonnecrotic cell death

Seed²,

Vos

et al. 1998

Prostate

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Arachidonic Acid Stimulates Prostate Cancer Cell Growth: Critical Role of 5-Lipoxygenase

Cited by 230 publications

References 26 publications

15-Lipoxygenase-2 (15-LOX-2) Is Expressed in Benign Prostatic Epithelium and Reduced in Prostate Adenocarcinoma

15-Lipoxygenase-2 (15-LOX-2) Is Expressed in Benign Prostatic Epithelium and Reduced in Prostate Adenocarcinoma

Modulation of Pulmonary Leukotriene B4 Production by Cyclooxygenase-2 Inhibitors and Lipopolysaccharide

5-lipoxygenase inhibitors reduce PC-3 cell proliferation and initiate nonnecrotic cell death

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