PC-SPES down-regulates COX-2 via inhibition of NF-κB and C/EBPβ in non-small cell lung cancer cells

Ikezoe, Takayuki; Yang, Yang; Saitoh, Takayuki; Heber, David; McKenna, Robert J.; Taguchi, Hirokuni; Koeffler, H. Phillip

doi:10.3892/ijo.29.2.453

Cited by 5 publications

(5 citation statements)

References 23 publications

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“…Those findings demonstrate that EMT is an important histopathological process in lung tumorigenesis. Interestingly, EMT of human lung epithelial cells could be medicated by C-EBPβ [31], which also participate tumorigenesis in lung [32]. Thus, C-EBPβ may be a potential target to prevent tumorigenesis of airway in the context of cigarette smoking.…”

Section: Discussionmentioning

confidence: 99%

C-EBPβ mediates in cigarette/IL-17A-induced bronchial epithelial–mesenchymal transition in COPD mice

Chu

et al. 2021

BMC Pulm Med

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Background Cigarettes smoking and IL-17A contribute to chronic obstructive pulmonary disease (COPD), and have synergistical effect on bronchial epithelial cell proliferation. CCAAT/enhancer-binding protein β (C-EBPβ) could be induced by IL-17A and is up-regulated in COPD. We explored the effect of cigarettes and IL-17 on bronchial epithelial–mesenchymal transition (EMT) in COPD mice and potential mechanism involved with C-EBPβ in this study. Methods COPD model was established with mice by exposing to cigarettes. E-Cadherin, Vimentin, IL-17A and C-EBPβ distributions were detected in lung tissues. Primary bronchial epithelial cells were separated from health mice and cocultured with cigarette smoke extract (CSE) or/and IL-17A. E-Cadherin, Vimentin and IL-17 receptor (IL-17R) expressions in vitro were assessed. When C-EBPβ were silenced by siRNA in cells, E-Cadherin, Vimentin and C-EBPβ expressions were detected. Results E-Cadherin distribution was less and Vimentin distribution was more in bronchus of COPD mice than controls. IL-17A and C-EBPβ expressions were higher in lung tissues of COPD mice than controls. In vitro, C-EBPβ protein expression was highest in CSE + IL-17A group, followed by CSE and IL-17A groups. E-cadherin expression in vitro was lowest and Vimentin expression was highest in CSE + IL-17A group, followed by CSE or IL-17A group. Those could be inhibited by C-EBPβ silenced. Conclusions C-EBPβ mediates in cigarette/IL-17A-induced bronchial EMT in COPD mice. Our findings contribute to a better understanding on the progress from COPD to lung cancers, which will provide novel avenues in preventing tumorigenesis of airway in the context of cigarette smoking.

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Section: Discussionmentioning

confidence: 99%

C-EBPβ mediates in cigarette/IL-17A-induced bronchial epithelial–mesenchymal transition in COPD mice

Chu

et al. 2021

BMC Pulm Med

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“…Likewise, aberrant COX-2 expression and a shift in the balance of vasodilatory and antiproliferative prostanoids have been demonstrated in animal models of pulmonary hypertension (13,14). In contrast, accumulating evidence points to an important role for COX-2 in carcinogenesis and tumor metastasis (15,16), as well as the injurious pulmonary response to acute infection (17,18). Evidence points to cyclooxygenase in the pathophysiology of ventilator-induced lung injury.…”

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confidence: 99%

The Role of Cyclooxygenase-2 in Mechanical Ventilation–Induced Lung Injury

Robertson

Sauer

Gold

et al. 2012

Am J Respir Cell Mol Biol

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Mechanical ventilation is necessary for patients with acute respiratory failure, but can cause or propagate lung injury. We previously identified cyclooxygenase-2 as a candidate gene in mechanical ventilationinduced lung injury. Our objective was to determine the role of cyclooxygenase-2 in mechanical ventilation-induced lung injury and the effects of cyclooxygenase-2 inhibition on lung inflammation and barrier disruption. Mice were mechanically ventilated at low and high tidal volumes, in the presence or absence of pharmacologic cyclooxygenase-2-specific inhibition with 3-(4-methylsulphonylphenyl)-4-phenyl-5-trifluoromethylisoxazole (CAY10404). Lung injury was assessed using markers of alveolar-capillary leakage and lung inflammation. Cyclooxygenase-2 expression and activity were measured by Western blotting, real-time PCR, and lung/plasma prostanoid analysis, and tissue sections were analyzed for cyclooxygenase-2 staining by immunohistochemistry. High tidal volume ventilation induced lung injury, significantly increasing both lung leakage and lung inflammation relative to control and low tidal volume ventilation. High tidal volume mechanical ventilation significantly induced cyclooxygenase-2 expression and activity, both in the lungs and systemically, compared with control mice and low tidal volume mice. The immunohistochemical analysis of lung sections localized cyclooxygenase-2 expression to monocytes and macrophages in the alveoli. The pharmacologic inhibition of cyclooxygenase-2 with CAY10404 significantly decreased cyclooxygenase activity and attenuated lung injury in mice ventilated at high tidal volume, attenuating barrier disruption, tissue inflammation, and inflammatory cell signaling. This study demonstrates the induction of cyclooxygenase-2 by mechanical ventilation, and suggests that the therapeutic inhibition of cyclooxygenase-2 may attenuate ventilator-induced acute lung injury. Keywords: cyclooxygenase-2; mechanical ventilation; lung injuryMechanical ventilation is a life-saving therapy for patients with acute respiratory failure. However, it can cause or worsen lung injury, particularly at larger tidal volumes (1, 2). Positive-pressure mechanical ventilation may expose the lungs, and particularly the alveoli, to overdistention, resulting in volutrauma with the subsequent release of inflammatory and vasoactive cytokines and prostanoids that propagate lung injury (1, 3). Therapeutic trials aimed at decreasing lung injury have focused on minimizing the damage from mechanical ventilation with the use of "protective" low tidal volume ventilator strategies. However, because of the heterogeneity of lung injury, even at lower tidal volumes, different regions of the lung may be subjected to higher stretch (4). Although using lower tidal volumes decreases markers of injury and inflammation and significantly improves survival in patients with acute lung injury, mortality remains high (1). A better understanding of the mechanisms by which mechanical ventilation injures the lungs will be key in identifying ...

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“…For example, Chinese herbal mixture denoted PC-SPES was shown to inhibit the growth of different kinds of cancer cells such as non-small cell lung cancer cells and prostate cancer cells (27,28). Recently, another herbal Rabdosia rubescens was reported to induce apoptosis of lung cancer cells or to inhibit the growth of breast cancer cells (29,30).…”

Section: Discussionmentioning

confidence: 99%

Serenoa repens induces growth arrest and apoptosis of human multiple myeloma cells via inactivation of STAT 3 signaling

Che

Hou²,

Kang³

et al. 2009

Oncol Rep

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Abstract. Serenoa repens, a palm species native to the Southeastern United States, is one of the widely used phytotherapeutic agents in benign prostatic hyperplasia. In this study, we found for the first time that Serenoa repens induced growth arrest of a variety of human leukemia cells including U266 and RPMI 8226 multiple myeloma cells as measured by mitochondrial-dependent conversion of the 3-(4, 5-dimethylthiazol-2-yl)-2, 5-diphenyltetrazolium bromide assay. TUNEL assays showed that Serenoa repens induced apoptosis of U266 cells in a time-and dose-dependent manner. Serenoa repens also increased the expression of cleaved-PARP or p27 protein in different human leukemia cell lines. In addition, we found that Serenoa repens down-regulated basal level of phosphorylated form of signal transducer and activator of transcription 3 (STAT 3) and Interleukin-6 induced level of phosphorylated form of STAT 3 and extracellular signal-related kinase (ERK) were also reduced after Serenoa repens treatment in U266 cells. Furthermore, we found that inhibition of STAT 3 signaling by Serenoa repens or Janus family of tyrosine kinase (JAK) inhibitor of AG490 enhanced the ability of docetaxel to inhibit the growth of U266 and RPMI 8226 cells, as measured by trypan blue exclusion test. These results indicate that Serenoa repens might be useful for the treatment of individuals with multiple myeloma.

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PC-SPES down-regulates COX-2 via inhibition of NF-κB and C/EBPβ in non-small cell lung cancer cells

Cited by 5 publications

References 23 publications

C-EBPβ mediates in cigarette/IL-17A-induced bronchial epithelial–mesenchymal transition in COPD mice

C-EBPβ mediates in cigarette/IL-17A-induced bronchial epithelial–mesenchymal transition in COPD mice

The Role of Cyclooxygenase-2 in Mechanical Ventilation–Induced Lung Injury

Serenoa repens induces growth arrest and apoptosis of human multiple myeloma cells via inactivation of STAT 3 signaling

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