Growth control of lung cancer by interruption of 5-lipoxygenase-mediated growth factor signaling.

Avis, Ingalill; Jett, Marti; Boyle, T; Vos, Michele D.; Moody, Terry W.; Treston, Anthony M.; Martı́nez, Alfredo; Mulshine, James L.

doi:10.1172/jci118480

Cited by 227 publications

(153 citation statements)

References 28 publications

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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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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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“…There is now increasing evidence of the possible involvement of lipoxygenases and their products in the regulation of cell growth and death. For example, inhibition of 5-LOX metabolism resulted in significant reduction in the growth of a number of lung cancer cell lines [25] and 5-LOX inhibitors such as 5,8,11,14-eicosatetraynoic acid, A63162 and SC41661A reduced the proliferation of chronic myelogenous leukaemia blast cells, induced their differentiation and promoted apoptosis in promyelocytic cells [26]. It was recently reported that the 12-LOX and probably the 15-and/or 5-LOX arachidonate pathways may function as critical regulators of cell survival and apoptosis in rat Walker 256 (W256) carcinosarcoma cells [27].…”

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confidence: 99%

Inhibition of ICE‐family cysteine proteases rescues murine lymphocytes from lipoxygenase inhibitor‐induced apoptosis

et al. 1996

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“…Such regulation might reflect the function of the enzyme in the nucleus, which is so far still unclear. Various studies have shown that 5LO is involved in cell proliferation [2][3][4][5][6][7], but the association of this function and the nuclear location of the enzyme has not been demonstrated. Further intracellular study of 5LO deficient in nucleotide binding might shed some light in this regard.…”

Section: Discussionmentioning

confidence: 99%

“…They have been implicated as mediators in asthma and other types of allergic reaction [1]. Recent reports have also shown that 5LO is involved in tumour cell proliferation [2][3][4][5][6][7] and is related to primary pulmonary hypertension [8][9][10][11][12].…”

Section: Introductionmentioning

confidence: 99%

Analysis of a nucleotide-binding site of 5-lipoxygenase by affinity labelling: binding characteristics and amino acid sequences

Hammarberg

Rådmark

Samuelsson

et al. 2000

Biochemical Journal

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5-Lipoxygenase (5LO) catalyses the first two steps in the biosynthesis of leukotrienes, which are inflammatory mediators derived from arachidonic acid. 5LO activity is stimulated by ATP ; however, a consensus ATP-binding site or nucleotidebinding site has not been found in its protein sequence. In the present study, affinity and photoaffinity labelling of 5LO with 5h-p-fluorosulphonylbenzoyladenosine (FSBA) and 2-azido-ATP showed that 5LO bound to the ATP analogues quantitatively and specifically and that the incorporation of either analogue inhibited ATP stimulation of 5LO activity. The stoichiometry of the labelling was 1.4 mol of FSBA\mol of 5LO (of which ATP competed with 1 mol\mol) or 0.94 mol of 2-azido-ATP\mol of 5LO (of which ATP competed with 0.77 mol\mol). Labelling with FSBA prevented further labelling with 2-azido-ATP, indicating that the same binding site was occupied by both analogues. Other nucleotides (ADP, AMP, GTP, CTP and UTP) also competed with 2-azido-ATP labelling, suggesting that the site

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Growth control of lung cancer by interruption of 5-lipoxygenase-mediated growth factor signaling.

Cited by 227 publications

References 28 publications

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

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

Inhibition of ICE‐family cysteine proteases rescues murine lymphocytes from lipoxygenase inhibitor‐induced apoptosis

Analysis of a nucleotide-binding site of 5-lipoxygenase by affinity labelling: binding characteristics and amino acid sequences

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