The role of COX-2 inhibitors in lung cancer

Qadri, S.; Wang, Jiag Huai; Redmond, Karen; O’Donnell, Aonghus; Aherne, Thomas; Redmond, H. P.

doi:10.1016/s0003-4975(02)04022-5

Cited by 32 publications

(15 citation statements)

References 11 publications

Supporting

Mentioning

Contrasting

Unclassified

Order By: Relevance

“…In addition, our data show that the selective COX-2 inhibitor rofecoxib is capable of inhibiting P-gp function because it induces R123 retention into TT cells and sensitizes both TT cells and MTC primary cultures to the cytotoxic effects of doxorubicin. Previous evidence showed that rofecoxib per se induces a dosedependent increase in apoptosis and growth inhibition in the Lewis lung tumor cell line in vitro (30). However, in our model, no cytotoxic effect of this compound was observed.…”

Section: Discussioncontrasting

confidence: 67%

Cyclooxygenase-2 Inhibitors Reverse Chemoresistance Phenotype in Medullary Thyroid Carcinoma by a Permeability Glycoprotein-Mediated Mechanism

Zatelli

Luchin

Piccin

et al. 2005

The Journal of Clinical Endocrinology &Amp; Metabolism

View full text Add to dashboard Cite

show abstract

Section: Discussioncontrasting

confidence: 67%

Cyclooxygenase-2 Inhibitors Reverse Chemoresistance Phenotype in Medullary Thyroid Carcinoma by a Permeability Glycoprotein-Mediated Mechanism

Zatelli

Luchin

Piccin

et al. 2005

The Journal of Clinical Endocrinology &Amp; Metabolism

View full text Add to dashboard Cite

show abstract

“…1A, pretreatment with the inhibitor of non-selective PKC (Ro318220), Ca 2+ -dependent PKC (Gö6983 and Gö6976), or selective PKCδ (Rottlerin) markedly attenuated ATPγS-induced COX-2 expression in A549 cells. COX-2 is the enzyme which converts arachidonic acid to PGH 2 , which can be further metabolized to prostanoids, including PGE 2 , prostacyclin (PGI 2 ), and thromboxane A 2 (TXA 2 ) [21]. Pretreatment with these inhibitors also attenuated ATPγS-induced COX-2 mRNA expression and PGE 2 generation (Fig.…”

Section: Resultsmentioning

confidence: 91%

ATP Mediates NADPH Oxidase/ROS Generation and COX-2/PGE2 Expression in A549 Cells: Role of P2 Receptor-Dependent STAT3 Activation

et al. 2013

View full text Add to dashboard Cite

BackgroundUp-regulation of cyclooxygenase (COX)-2 and its metabolite prostaglandin E2 (PGE2) are frequently implicated in lung inflammation. Extracellular nucleotides, such as ATP have been shown to act via activation of P2 purinoceptors, leading to COX-2 expression in various inflammatory diseases, such as lung inflammation. However, the mechanisms underlying ATP-induced COX-2 expression and PGE2 release remain unclear.Principal FindingsHere, we showed that ATPγS induced COX-2 expression in A549 cells revealed by western blot and real-time PCR. Pretreatment with the inhibitors of P2 receptor (PPADS and suramin), PKC (Gö6983, Gö6976, Ro318220, and Rottlerin), ROS (Edaravone), NADPH oxidase [diphenyleneiodonium chloride (DPI) and apocynin], Jak2 (AG490), and STAT3 [cucurbitacin E (CBE)] and transfection with siRNAs of PKCα, PKCι, PKCμ, p47phox, Jak2, STAT3, and cPLA2 markedly reduced ATPγS-induced COX-2 expression and PGE2 production. In addition, pretreatment with the inhibitors of P2 receptor attenuated PKCs translocation from the cytosol to the membrane in response to ATPγS. Moreover, ATPγS-induced ROS generation and p47phox translocation was also reduced by pretreatment with the inhibitors of P2 receptor, PKC, and NADPH oxidase. On the other hand, ATPγS stimulated Jak2 and STAT3 activation which were inhibited by pretreatment with PPADS, suramin, Gö6983, Gö6976, Ro318220, GF109203X, Rottlerin, Edaravone, DPI, and apocynin in A549 cells.SignificanceTaken together, these results showed that ATPγS induced COX-2 expression and PGE2 production via a P2 receptor/PKC/NADPH oxidase/ROS/Jak2/STAT3/cPLA2 signaling pathway in A549 cells. Increased understanding of signal transduction mechanisms underlying COX-2 gene regulation will create opportunities for the development of anti-inflammation therapeutic strategies.

show abstract

“…Although the benefit of aspirin for patients with cancer has been widely appreciated, the mechanism behind remains largely unclear. Previous understandings tend to attribute the anticancer potential of aspirin to the inhibition of cyclooxygenase-2 (COX-2), which is upregulated in various cancer cells (10,11). Of note, increasing evidence has suggested that aspirin may exhibit anticancer effects in a COX-independent manner.…”

Section: Introductionmentioning

confidence: 99%

Aspirin Inhibits Cancer Metastasis and Angiogenesis via Targeting Heparanase

Dai

Yan

et al. 2017

Clinical Cancer Research

104

View full text Add to dashboard Cite

Purpose: Recent epidemiological and clinical studies have suggested the benefit of aspirin for patients with cancer, which inspired increasing efforts to demonstrate the anticancer ability of aspirin and reveal the molecular mechanisms behind. Nevertheless, the anticancer activity and related mechanisms of aspirin remain largely unknown. This study aimed to confirm this observation, and more importantly, to investigate the potential target contributed to the anticancer of aspirin.Experimental Design: A homogeneous time-resolved fluorescence (HTRF) assay was used to examine the impact of aspirin on heparanase. Streptavidin pull-down, surface plasmon resonance (SPR) assay, and molecular docking were performed to identify heparanase as an aspirin-binding protein. Transwell, rat aortic rings, and chicken chorioallantoic membrane model were used to evaluate the antimetastasis and anti-angiogenesis effects of aspirin, and these phenotypes were tested in a B16F10 metastatic model, MDA-MB-231 metastatic model, and MDA-MB-435 xenograft model.Results: This study identified heparanase, an oncogenic extracellular matrix enzyme involved in cancer metastasis and angiogenesis, as a potential target of aspirin. We had discovered that aspirin directly binds to Glu225 region of heparanase and inhibits the enzymatic activity. Aspirin impeded tumor metastasis, angiogenesis, and growth in heparanase-dependent manner.Conclusions: In summary, this study has illustrated heparanase as a target of aspirin for the first time. It provides insights for a better understanding of the mechanisms of aspirin in anticancer effects, and offers a direction for the development of smallmolecule inhibitors of heparanase.

show abstract

The role of COX-2 inhibitors in lung cancer

Cited by 32 publications

References 11 publications

Cyclooxygenase-2 Inhibitors Reverse Chemoresistance Phenotype in Medullary Thyroid Carcinoma by a Permeability Glycoprotein-Mediated Mechanism

Cyclooxygenase-2 Inhibitors Reverse Chemoresistance Phenotype in Medullary Thyroid Carcinoma by a Permeability Glycoprotein-Mediated Mechanism

ATP Mediates NADPH Oxidase/ROS Generation and COX-2/PGE2 Expression in A549 Cells: Role of P2 Receptor-Dependent STAT3 Activation

Aspirin Inhibits Cancer Metastasis and Angiogenesis via Targeting Heparanase

Contact Info

Product

Resources

About