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

Mao, Jenny T.; Tsu, I-Hsien; Dubinett, Steven M.; Adams, Bradley J.; Sarafian, Theodore A.; Baratelli, Felicita; Roth, Michael D.; Serio, Kenneth J.

doi:10.1158/1078-0432.ccr-04-0945

Cited by 46 publications

(39 citation statements)

References 36 publications

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“…The lung is the most likely source for elevated PGE 2 synthesis because of its immense surface area and the known link between tobacco smoke and pulmonary inflammation. Inflammation is associated with increased production of PGE 2 (45,46) and various cell types within the lung have the capacity to produce large amounts of PGE 2 in response to proinflammatory stimuli (47,48). In support of this idea, increased levels of exhaled PGE 2 have been detected in patients with chronic obstructive pulmonary disease versus healthy controls (49).…”

Section: Discussionmentioning

confidence: 99%

Levels of Prostaglandin E Metabolite, the Major Urinary Metabolite of Prostaglandin E2, Are Increased in Smokers

Gross¹,

Boyle²,

Morrow

et al. 2005

Clinical Cancer Research

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Purpose: Increased levels of cyclooxygenase-2 and prostaglandin E 2 (PGE 2 ) have been observed in tobacco-related malignancies of the upper aerodigestive tract. Moreover, exposure to tobacco smoke can stimulate the synthesis of PGE 2 . Recent evidence suggests that urinary PGE metabolite (PGE-M) can be used as an index of systemic PGE 2 production. In this study, we investigated whether levels of urinary PGE-M were increased in smokers and in patients with head and neck squamous cell carcinoma (HNSCC). Experimental Design: Fifty-eight HNSCC cases and 29 age-and gender-matched healthy controls were prospectively enrolled in the study. A detailed smoking history and single void urine specimen were obtained from each participant. Levels of urinary PGE-M were quantified in a blinded fashion using mass spectrometry and compared with smoking history and tumor status. Results: Adjusted for case-control matching, median urinary PGE-M levels were significantly higher in ever smokers (15.7 ng/mg creatinine) compared with never smokers (9.9 ng/mg creatinine) for the entire study population (n = 87, P = 0.005). Concentrations of urinary PGE-M were nearly doubled in ever smokers (15.2 ng/mg creatinine) versus never smokers (7.8 ng/mg creatinine) among healthy controls (P = 0.001). Higher PGE-M levels were observed in current versus former smokers and in those with greater pack-year exposure. A significant difference in amounts of PGE-M was not observed in patients with HNSCC versus healthy controls. Conclusions: Increased levels of urinary PGE-M were observed in smokers. Urinary PGE-M may have use as a noninvasive biomarker of the effects of tobacco smoke exposure.

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Section: Discussionmentioning

confidence: 99%

Levels of Prostaglandin E Metabolite, the Major Urinary Metabolite of Prostaglandin E2, Are Increased in Smokers

Gross¹,

Boyle²,

Morrow

et al. 2005

Clinical Cancer Research

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“…The primers for PCR were designed based on GenBank for annexin A1 (annexin-I) mRNA sequences NM_000700, 18 and b-actin mRNA sequences CR608667. 19 The primer sequences for b-actin was sense, 5 0 -GTACCACTGGCATCGTGAT-3 0 , antisense: 5 0 -ATCTTCATGAGGTAGTCAGTCA-3 0 . The primer sequence for annexin-I was: sense, 5 0 -AAAGGTGGTCCCGG ATCAAG-3 0 , antisense, 5 0 -TTATGCAAGGCAGCGACATC-3 0 .…”

Section: Rna Extraction and Quantitative Real-time Rt-pcrmentioning

confidence: 99%

Green tea induces annexin-I expression in human lung adenocarcinoma A549 cells: involvement of annexin-I in actin remodeling

Jin

Zhang

et al. 2007

Laboratory Investigation

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Green tea polyphenols exhibit multiple antitumor activities in various in vitro and in vivo tumor models, and the mechanisms of action are not clear. Previously, we found that green tea extract (GTE) regulates actin remodeling in different cell culture systems. Actin remodeling plays an important role in cancer cell morphology, cell adhesion, motility, and invasion. Using proteomic approaches, we found GTE-induced expression of annexin-I, a multifunctional actin binding protein, in these cell lines. In this study, we aimed to further define the functional role of GTE-induced annexin-I expression in actin remodeling, cell adhesion, and motility in lung adenocarcinoma A549 cells. We found that GTE stimulates the expression of annexin-I in a dose-dependent fashion. The GTE-induced annexin-I expression appears to be at the transcription level, and the increased annexin-I expression mediates actin polymerization, resulting in enhanced cell adhesion and decreased motility. Annexin-I specific interference resulted in loss of GTE-induced actin polymerization and cell adhesion, but not motility. In fact, annexin-I specific interference itself inhibited motility even without GTE. Together, annexin-I plays an important role in GTE-induced actin remodeling, and it may serve as a potential molecular target associated with the anticancer activities of green tea.

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“…Thus, a case can be considered where inhibition of COX-2 could shift arachidonic acid to the LOX pathway, thereby suppressing apoptosis-not a desirable effect in cancer prevention. A recent human study suggested that oral celecoxib increased leukotriene B 4 production in the lung microenvironment under physiologic conditions, although the functional significance of this effect was uncertain (Mao et al, 2004).…”

Section: Consmentioning

confidence: 99%

Cancer Prevention: A New Era beyond Cyclooxygenase-2

Rigas¹,

Kashfi²

2005

J Pharmacol Exp Ther

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The seminal epidemiological observation that nonsteroidal antiinflammatory drugs (NSAIDs) prevent colon and possibly other cancers has spurred novel approaches to cancer prevention. The known inhibitory effect of NSAIDs on the eicosanoid pathway prompted studies focusing on cyclooxygenase (COX) and its products. The increased prostaglandin E 2 levels and the overexpression of COX-2 in colon and many other cancers provided the rationale for clinical trials with COX-2 inhibitors for cancer prevention or treatment. Their efficacy in the prevention of sporadic colon and other cancers remains unknown; one COX-2 inhibitor has been withdrawn because of side effects, and there are concerns about whether these effects are class-specific. There is evidence to suggest that COX-2 may not be the only or ideal eicosanoid pathway target for cancer prevention. Six sets of observations support this notion: the relatively late induction of COX-2 during carcinogenesis; the finding that NSAIDs may not require inhibition of COX-2 for their effect; the modest effect of coxibs in cancer prevention; that currently available coxibs have multiple non-COX-2 effects that may account for at least some of their efficacy; the possibility that concurrent inhibition of COX-2 in non-neoplastic cells may be harmful; and the possibility that COX-2 inhibition may modulate alternative eicosanoid pathways in a way that promotes carcinogenesis. Given the limitations of COX-2-specific inhibitors and the biological evidence mentioned above, we suggest that targets other than COX-2 should be pursued as alternative or complementary approaches to cancer prevention.Cancer, a major medical challenge during the last 100 years, has touched the life of almost every American family and absorbs an inordinate amount of health care resources. In the US, cancer has moved to first place among the causes of death, surpassing cardiovascular disease. That cancer prevention is better than treatment is almost axiomatic in medicine. In contrast to cardiovascular and infectious diseases, whose prevention has had a substantial impact on their associated morbidity and mortality, gains in cancer prevention have been limited. The main reasons for this can be found in two areas: the identification of informative biomarkers and the development of safe and effective chemopreventive agents. In this perspective, we present a brief overview of current efforts to develop effective chemopreventive drugs focused on cyclooxygenase (COX) inhibition, and, taking a rather iconoclastic approach, we suggest that a search for alternative targets for drug development may be in order.

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

Cited by 46 publications

References 36 publications

Levels of Prostaglandin E Metabolite, the Major Urinary Metabolite of Prostaglandin E2, Are Increased in Smokers

Levels of Prostaglandin E Metabolite, the Major Urinary Metabolite of Prostaglandin E2, Are Increased in Smokers

Green tea induces annexin-I expression in human lung adenocarcinoma A549 cells: involvement of annexin-I in actin remodeling

Cancer Prevention: A New Era beyond Cyclooxygenase-2

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