Overexpression of cyclooxygenase-2 in NCI-H292 human alveolar epithelial carcinoma cells: Roles of p38 MAPK, ERK-1/2, and PI3K/PKB signaling proteins

Sung, Su-Haeng; Park, Yukyoung; Jo, Jeong-Rang; Jung, Nak-Kyun; Song, Dae‐Kyu; Bae, Jae‐Hoon; Keum, Dong-Yun; Kim, Jae-Bum; Park, Gy-Young; Jang, Byeong‐Churl; Park, Jong‐Wook

doi:10.1002/jcb.23226

Cited by 18 publications

(14 citation statements)

References 47 publications

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“…5A, lanes 1-5). In a recent study, we demonstrated the serum-dependent induction of COX-2 expression in NCI-H292 cells, a human laryngeal cell line (29). As shown in Fig.…”

Section: Bai Is Also Capable Of Inhibiting Phorbol-12-myristate-13-acmentioning

confidence: 69%

BAI, a 3-aminoindazole derivative, inhibits interleukin-1β-induced expression of cyclooxygenase-2 in A549 human airway cells

Hong

Park²,

Park³

et al. 2011

Int J Mol Med

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Abstract. Cyclooxygenase (COX)-2 and its products, including PGE 2 , are key inflammatory mediators. In this study, we have assessed the pharmacological characteristics of BAI, a 3-aminoindazole derivative and a novel cyclin-dependent kinase (CDK) inhibitor, for regulation of COX-2 expression induced by interleukin (IL)-1β in A549 human airway cells. Treatment with BAI strongly inhibited IL-1β-induced expression of COX-2 at both the protein and mRNA levels. Results of luciferase experiments also revealed that BAI treatment reduced IL-1β-induced COX-2 promoter activity. Distinctly, treatment with BAI did not affect IL-1β-induced phosphorylation of extracellular signal-regulated protein kinase-1/2 (ERK-1/2), p38 mitogen-activated protein kinase (MAPK), and c-Jun N-terminal protein kinase-1/2 (JNK-1/2) and proteolysis of IκB-α, an inhibitor of nuclear factor (NF)-κB, but inhibited IL-1β-induced phosphorylation of histone H1, a target for phosphorylation by CDKs. siRNA transfection experiments demonstrated that knockdown of CDK2 and CDK4 led to a slight reduction of IL-1β-induced histone H1 phosphorylation but had no effect on IL-1β-induced COX-2 expression. Interestingly, additional cell culture experiments showed the ability of BAI to repress the PMA-induced COX-2 expression in A549 cells and serum-dependent COX-2 expression in NCI-H292 cells, a human laryngeal cell line. Collectively, these results demonstrate firstly that BAI downregulates IL-1β-induced COX-2 expression through transcriptional repression, which appears to be independent of CDK2, CDK4, MAPKs and NF-κB, in A549 cells. It is suggested that BAI may be a potential candidate for treatment of the airway inflammatory diseases where COX-2 overexpression is problematic.

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“…5A, lanes 1-5). In a recent study, we demonstrated the serum-dependent induction of COX-2 expression in NCI-H292 cells, a human laryngeal cell line (29). As shown in Fig.…”

Section: Bai Is Also Capable Of Inhibiting Phorbol-12-myristate-13-acmentioning

confidence: 69%

BAI, a 3-aminoindazole derivative, inhibits interleukin-1β-induced expression of cyclooxygenase-2 in A549 human airway cells

Hong

Park²,

Park³

et al. 2011

Int J Mol Med

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“…In H292 cells, culture medium containing 10% serum alone (without LPS) strongly up-regulates COX-2 expression (34). Here 2% FBS was used to reduce, but not eliminate, the background signaling for which serum components are co-factors and to demonstrate the suppression of LPS-stimulated signaling by heparin.…”

Section: Discussionmentioning

confidence: 99%

Heparin and LPS-induced COX-2 expression in airway cells: a link between its anti-inflammatory effects and GAG sulfation

Newman

Zhang

et al. 2015

Experimental Lung Research

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Purpose/Aim Previous studies have indicated that the sulfated polysaccharide heparin has anti-inflammatory effects. However, the mechanistic basis for these effects has not been fully elucidated. Materials and Methods NCI-H292 (mucoepidermoid) and HBE-1 (normal) human bronchial epithelial cells were treated with LPS alone or in the presence of high-molecular-weight (HMW) fully-sulfated heparin or desulfated HMW heparin. Cells were harvested to examine the phosphorylation levels of ERK1/2, p38, and NF-κB p65 and COX-2 protein expression by Western blot and gene expression of both COX-2 and CXCL-8 by TaqMan qRT-PCR. Results Heparin is known to exert an influence on receptor-mediated signaling through its ability to both potentiate and inhibit the receptor-ligand interaction, depending upon its concentration. In H292 cells, fully-sulfated HMW heparin significantly reduced LPS-induced gene expression of both COX-2 and CXCL-8 for up to 48 hours, while desulfated heparin had little to no significant suppressive effect on signaling or on COX-2 gene or protein expression. Desulfated heparin, initially effective at preventing LPS-induced CXCL8 up-regulation, reduced CXCL8 transcription at 24 hours. In contrast, in normal HBE-1 cells, fully-sulfated heparin significantly suppressed only ERK signaling, COX-2 gene expression at 12 hours, and CXCL-8 gene expression at 6 and 12 hours, while desulfated heparin had no significant effects on LPS-stimulated signaling or on gene or protein expression. Sulfation determines heparin’s influence and may reflect the moderating role of GAG sulfation in lung injury and health. Conclusions Heparin’s anti-inflammatory effects result from its non-specific suppression of signaling and gene expression and are determined by its sulfation.

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“…COX-1 is up-regulated in cervical, ovarian and gallbladder cancers [1]. COX-2, which is normally undetectable in healthy tissue, is markedly over-expressed in colorectal, lung [76], prostate [77], cervical [78], ovarian [79], breast, gastric, pancreatic [80] and certain head and neck squamous cell [81] cancers. In the following paragraphs, we will examine the involvements of COXs in tumor initiation and progression in more depth.…”

Section: Cyclooxygenases and Cancermentioning

confidence: 99%

Non-steroid anti-inflammatory drugs, prostaglandins, and cancer

2013

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Fatty acids are involved in multiple pathways and play a pivotal role in health. Eicosanoids, derived from arachidonic acid, have received extensive attention in the field of cancer research. Following release from the phospholipid membrane, arachidonic acid can be metabolized into different classes of eicosanoids through cyclooxygenases, lipoxygenases, or p450 epoxygenase pathways. Non-steroid anti-inflammatory drugs (NSAIDs) are widely consumed as analgesics to relieve minor aches and pains, as antipyretics to reduce fever, and as anti-inflammatory medications. Most NSAIDs are nonselective inhibitors of cyclooxygenases, the rate limiting enzymes in the formation of prostaglandins. Long term use of some NSAIDs has been linked with reduced incidence and mortality in many cancers. In this review, we appraise the biological activities of prostanoids and their cognate receptors in the context of cancer biology. The existing literature supports that these lipid mediators are involved to a great extent in the occurrence and progression of cancer.

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Overexpression of cyclooxygenase-2 in NCI-H292 human alveolar epithelial carcinoma cells: Roles of p38 MAPK, ERK-1/2, and PI3K/PKB signaling proteins

Cited by 18 publications

References 47 publications

BAI, a 3-aminoindazole derivative, inhibits interleukin-1β-induced expression of cyclooxygenase-2 in A549 human airway cells

BAI, a 3-aminoindazole derivative, inhibits interleukin-1β-induced expression of cyclooxygenase-2 in A549 human airway cells

Heparin and LPS-induced COX-2 expression in airway cells: a link between its anti-inflammatory effects and GAG sulfation

Non-steroid anti-inflammatory drugs, prostaglandins, and cancer

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