Secretory Phospholipase A2 Inhibition Attenuates Intercellular Adhesion Molecule-1 Expression in Human Esophageal Adenocarcinoma Cells

Sadaria, Miral R.; Meng, Xianzhong; Fullerton, David A.; Reece, T. Brett; Shah, Roopali R.; Grover, Frederick L.; Weyant, Michael J.

doi:10.1016/j.athoracsur.2011.01.017

Cited by 32 publications

(19 citation statements)

References 24 publications

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“…Additional studies are needed to determine whether this observation has implications for the effect of sPLA 2 IIa inhibition on downstream NF- κ B targets such as metastasis-associated adhesion molecules and expression of inducible growth factors. 5,14–17 …”

Section: Discussionmentioning

confidence: 99%

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Group IIa secretory phospholipase expression correlates with group IIa secretory phospholipase inhibition–mediated cell death in K-ras mutant lung cancer cells

Meng

et al. 2012

The Journal of Thoracic and Cardiovascular Surgery

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Objective There are currently no targeted therapies against lung tumors with oncogenic K-ras mutations that are found in 25% to −40% of lung cancers and are characterized by their resistance to epidermal growth factor receptor inhibitors. The isozyme group IIa secretory phospholipase A2 (sPLA2IIa) is a potential biomarker and regulator of lung cancer cell invasion; however, the relationship between K-ras mutations and sPLA2IIa has yet to be investigated. We hypothesize that sPLA2IIa modulates lung cancer cell growth in K-ras mutant cells and that sPLA2IIa expression in human lung tumors is increased in K-ras mutant tumors. Methods Baseline sPLA2IIa expression in K-ras mutant lung cancer cell lines (A549, SW1573, H358, H2009) was assessed. Cells were treated with a specific sPLA2IIa inhibitor and evaluated for apoptosis and cell viability. Nuclear factor kappa-b (NF-κB) and extracellular signal-regulated kinase 1/2 activity were detected by Western blot. Human tumor samples were evaluated for sPLA2IIa mRNA expression by quantitative reverse-transcription polymerase chain reaction. Results Cytotoxicity of sPLA2IIa inhibition correlates with sPLA2IIa expression. Apoptosis in response to sPLA2 inhibition parallels attenuation in NF-κB activity. In addition, sPLA2IIa expression in human tumors correlates with squamous cell pathology and increasing stage of K-ras mutant lung tumors. Conclusions Baseline sPLA2IIa expression predicts response to sPLA2IIa inhibition in some K-ras mutant lung cancer cells. This finding is independent of p53 mutation status. Furthermore, squamous tumors and advanced-stage K-ras mutant tumors express more sPLA2IIa. These data support a role for sPLA2IIa as a potential global therapeutic target in the treatment of lung cancer.

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Section: Discussionmentioning

confidence: 99%

“…14,19,20 Mechanistic investigation of how sPLA 2 IIa effects production of tumor-promoting eicosanoids, including its interactions with other phospholipase enzymes, is ongoing. In addition, sPLA 2 IIa is a secreted molecule with potential autocrine and paracrine signaling capability.…”

Section: Discussionmentioning

confidence: 99%

Group IIa secretory phospholipase expression correlates with group IIa secretory phospholipase inhibition–mediated cell death in K-ras mutant lung cancer cells

Meng

et al. 2012

The Journal of Thoracic and Cardiovascular Surgery

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“…16 Evidence suggests that sPLA2 IIa modulates NF- κ B, as ICAM-1 and sPLA2 IIa, both NF- κ B target genes, are downregulated when sPLA2 IIa is inhibited. 3,4,12 …”

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Knockdown of secretory phospholipase A2 IIa reduces lung cancer growth in vitro and in vivo

Mauchley

et al. 2012

The Journal of Thoracic and Cardiovascular Surgery

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Objective Group IIa secretory phospholipase A2 (sPLA2 IIa) plays a role in the malignant potential of several epithelial cancers. Nuclear factor kappa B (NF-κB) regulates cancer cell growth and is modulated by phospholipase activity in many cancer cells. We hypothesized that knockdown of sPLA2 in lung cancer cells would reduce cell proliferation and NF-κB activity in vitro and attenuate tumor growth in vivo. Methods Two human non–small cell lung cancer cell lines (A549 and H358) were transduced with short hairpin RNA targeting sPLA2 group IIa. Quantitative reverse transcriptase-polymerase chain reaction and immunoblotting confirmed knockdown of sPLA2 IIa messenger RNA and protein, respectively. Cell proliferation was evaluated by the 5-bromo-2′-deoxyuridine DNA labeling assay. NF-κB phosphorylation was assayed by western blot. 1 × 106 of A549 or A549 sPLA2 knockdown cells were injected into the left flanks of nude mice (aged 6 to 8 weeks). Tumors were followed for 23 days, then removed and stained with hematoxylin and eosin, stained with Ki-67, and analyzed for sPLA2 IIa messenger RNA expression. Results sPLA2 knockdown reduced NF-κB phosphorylation and tumor growth in vivo. A549 wild-type tumors grew twice as fast as knockdown tumors. Ki-67 staining was more prominent throughout the wild-type tumors compared with knockdown tumors. Explanted knockdown tumors maintained lower sPLA2 levels compared with wild-type, confirmed by reverse transcriptase-polymerase chain reaction. Conclusions Knockdown of sPLA2 IIa suppresses lung cancer growth in part by attenuating NF-κB activity. These findings justify further investigation into the cellular mechanisms of sPLA2 in lung cancer and its potential role as a therapeutic target.

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“…sPLA 2 isoforms produce inflammatory mediators that stimulate the expression of ICAM-1. Recently several studies have looked beyond the role of phospholipase enzymes in inflammation to probe their contribution to the pathogenesis of cancer [25][26][27]. As per our knowledge there is no study that has determined the status of PLA 2 isoforms expression in colon cells after exposure with B(α)P. There are some studies that have reported the expression of various PLA 2 isoforms in some cancers including colon cancer.…”

Section: Discussionmentioning

confidence: 99%

Phospholipase A2 Isoforms in Benzo (α) Pyrene-Induced Molecular Changes in Colon Cancer Cells: A Plausible Therapeutic Target

Sharma¹,

Yadav²,

Sharma³

et al. 2020

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Background: Colorectal cancer (CRC) is the third most common cancer prevalent in men, and the second in women worldwide. The exact cause and pathogenesis of this disease remains unknown. In every cell multiple phospholipase A2 (PLA2) exists, but their contribution to the cell function has yet not been determined. The increased activity of these isoforms may be important in the generation of inflammatory mediators which finally are involved in the initiation of carcinogenesis. This study has explored the pathways involved in the differential response of HCT-15 and HT-29 colon cell lines during benzo(α)pyrene [B(α)P]-induced molecular changes.Methods: HT-29 and HCT-15 cells were used for the present study. Benzo(α)pyrene [B(α)P]-induced molecular changes were evaluated through cell viability using MTT assay, reactive oxygen species (ROS) measurement using 2,7 dichloro-dihydro-fluorescin diacetate (DCFH-DA), The gene expressions of PLA2 isoforms were estimated by RT- PCR. Further, knockdown of PLA2 isoform in transfected cells was done with siRNA.Results: The cell viability decreased significantly after exposure with B(α)P in both cell lines. Reactive oxygen species (ROS) production after exposure with B(α)P was significantly induced in both types of colon cell lines. The gene expressions of PLA2 isoforms were also estimated. Three PLA2 isoforms such as IB and, IID, IVA were induced after exposure with B(α)P respectively in HT -29 and HCT-15 cell lines. Further, a significant knockdown of PLA2 isoform in transfected cells with siRNA, and B(α)P exposure was observed in HCT-15 and HT-29 cells. There was a significant induction of ROS in IVA transfected HCT-15 cells exposure with B(α)P.Conclusion: It is concluded that each cell line behaved differently, specific PLA2 siRNA are involved in controlling the cascades related ROS, depending upon the origin of the cells. Secretary phospholipase A2 (sPLA2) inhibitors are likely to have a therapeutic potential in colon pathologies.

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Secretory Phospholipase A2 Inhibition Attenuates Intercellular Adhesion Molecule-1 Expression in Human Esophageal Adenocarcinoma Cells

Cited by 32 publications

References 24 publications

Group IIa secretory phospholipase expression correlates with group IIa secretory phospholipase inhibition–mediated cell death in K-ras mutant lung cancer cells

Group IIa secretory phospholipase expression correlates with group IIa secretory phospholipase inhibition–mediated cell death in K-ras mutant lung cancer cells

Knockdown of secretory phospholipase A2 IIa reduces lung cancer growth in vitro and in vivo

Phospholipase A2 Isoforms in Benzo (α) Pyrene-Induced Molecular Changes in Colon Cancer Cells: A Plausible Therapeutic Target

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