Cyclooxygenase-2, Epidermal Growth Factor Receptor, and Aromatase Signaling in Inflammation and Mesothelioma

Nuvoli, Barbara; Galati, Rossella

doi:10.1158/1535-7163.mct-12-1103

Cited by 21 publications

(24 citation statements)

References 87 publications

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“…There are currently no approved second-line treatments for patients who do not respond to the chemotherapy regimen indicating an urgent need for the development of more effective therapies and a better understanding of this malignancy. Previous studies have demonstrated the potential role of COX-2 as a therapeutic target in MPM [4,[43][44][45] and the selective COX-2 inhibitor celecoxib has been included, in combination with other drugs, in clinical trials for patients with MPM [46]. In the current study we have demonstrated that the 5-LOX and 12-LOX proteins are expressed in a significant proportion of MPM samples (73% and 83% respectively) and may represent novel therapeutic targets in this disease.…”

Section: Discussionsupporting

confidence: 55%

The Investigation of Lipoxygenases as Therapeutic Targets in Malignant Pleural Mesothelioma

Oguh-Olayinka

Agarwal

Ranatunge

et al. 2019

Pathol. Oncol. Res.

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Advanced malignant pleural mesothelioma (MPM) has an extremely poor prognosis with limited chemotherapy options, therefore the identification of new therapeutic targets would aid in disease management. Arachidonic acid is metabolised by cyclooxygenase and lipoxygenase enzymes. The lipoxygenase isoenzymes 5-LOX and 12-LOX have been implicated in carcinogenesis. We aimed to examine 5-LOX and 12-LOX protein expression in a large retrospective series of mesothelioma samples. Further to this, the in vitro cytotoxic effects of lipoxygenase pathway inhibitors were investigated in mesothelioma cells. Archival samples from 83 patients with MPM were examined by immunohistochemistry for expression of the 5-LOX and 12-LOX proteins. The MTS assay was used to assess cell viability following 72 h treatment with the lipoxygenase pathway inhibitors baicalein, licofelone, MK-886 and zileuton in the MPM cell lines NCI-H2052, NCI-H2452 and MSTO-211H. Positive 12-LOX protein expression was recorded in 69/83 (83%) and positive 5-LOX expression was observed in 56/77 (73%) of MPM tissue samples. Co-expression of 5-LOX with 12-LOX was seen in 46/78 (58%) of MPM samples. Positive expression of 5-LOX, 12-LOX and COX-2 proteins was identified in the NCI-H2052, NCI-H2452 and MSTO-211H MPM cell lines. Baicalein (12-LOX and 15-LOX inhibitor) was effective in 3/3 MPM cell lines at low concentrations with an IC50 range of 9.6 μM to 20.7 μM. We have demonstrated that the 5-LOX and 12-LOX proteins are expressed in a significant proportion of MPM samples (73% and 83% respectively) and may represent novel therapeutic targets in this disease. We have demonstrated that the inhibition of the LOX pathway using baicalein may be effective as a novel treatment for MPM, however further human pharmacokinetic studies are required in order to establish whether the concentration used in vitro is clinically achievable.

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Section: Discussionsupporting

confidence: 55%

The Investigation of Lipoxygenases as Therapeutic Targets in Malignant Pleural Mesothelioma

Oguh-Olayinka

Agarwal

Ranatunge

et al. 2019

Pathol. Oncol. Res.

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“…Its expression is induced by pro-inflammatory cytokines such as interleukin (IL)-1β, tumor necrosis factor-α (TNF-α), monocyte chemoattractant protein-1 (MCP-1), and myeloperoxidase (MPO). COX-2 is an oxygenase that plays a key role in the promotion and development of inflammatory responses [30]. COX-2 contains a cyclic AMP response element, a nuclear factor kappa B (NF-kappa B) binding site, and a nuclear factor for IL-6/CCAAT enhancer-binding protein (NF-IL6/C/EBP) sequence [6].…”

Section: Introductionmentioning

confidence: 99%

Exercise suppresses COX-2 pro-inflammatory pathway in vestibular migraine

Lee

Yi²,

Huang

et al. 2015

Brain Research Bulletin

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“…Obesity leads to elevated expression of insulin, estrogen, growth factors, inflammatory cytokines and adipokines, which promote ovarian cancer cell proliferation, survival, metastasis, angiogenesis and reduced apoptosis in cancer cells. Obesity-associated inflammation is thought to be one of the most important factors connecting obesity to cancer [19, 48, 49]. Multiple lines of preclinical evidence demonstrate that COX-2 contributes to obesity and obesity-induced muscular insulin resistance [48].…”

Section: Discussionmentioning

confidence: 99%

The effect of celecoxib on tumor growth in ovarian cancer cells and a genetically engineered mouse model of serous ovarian cancer

et al. 2016

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Our objective was to evaluate the effect of the COX-2 inhibitor, celecoxib, on (1) proliferation and apoptosis in human ovarian cancer cell lines and primary cultures of ovarian cancer cells, and (2) inhibition of tumor growth in a genetically engineered mouse model of serous ovarian cancer under obese and non-obese conditions. Celecoxib inhibited cell proliferation in three ovarian cancer cell lines and five primary cultures of human ovarian cancer after 72 hours of exposure. Treatment with celecoxib resulted in G1 cell cycle arrest, induction of apoptosis, inhibition of cellular adhesion and invasion and reduction of expression of hTERT mRNA and COX-2 protein in all of the ovarian cancer cell lines. In the KpB mice fed a high fat diet (obese) and treated with celecoxib, tumor weight decreased by 66% when compared with control animals. Among KpB mice fed a low fat diet (non-obese), tumor weight decreased by 46% after treatment with celecoxib. In the ovarian tumors from obese and non-obese KpB mice, treatment with celecoxib as compared to control resulted in decreased proliferation, increased apoptosis and reduced COX-2 and MMP9 protein expression, as assessed by immunohistochemistry. Celecoxib strongly decreased the serum level of VEGF and blood vessel density in the tumors from the KpB ovarian cancer mouse model under obese and non-obese conditions. This work suggests that celecoxib may be a novel chemotherapeutic agent for ovarian cancer prevention and treatment and be potentially beneficial in both obese and non-obese women.

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Cyclooxygenase-2, Epidermal Growth Factor Receptor, and Aromatase Signaling in Inflammation and Mesothelioma

Cited by 21 publications

References 87 publications

The Investigation of Lipoxygenases as Therapeutic Targets in Malignant Pleural Mesothelioma

The Investigation of Lipoxygenases as Therapeutic Targets in Malignant Pleural Mesothelioma

Exercise suppresses COX-2 pro-inflammatory pathway in vestibular migraine

The effect of celecoxib on tumor growth in ovarian cancer cells and a genetically engineered mouse model of serous ovarian cancer

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