Apigenin and Wogonin Regulate Epidermal Growth Factor Receptor Signaling Pathway Involved in MUC5AC Mucin Gene Expression and Production from Cultured Airway Epithelial Cells

Sikder, Md. Asaduzzaman; Lee, Hyun Jae; Ryu, Jiho; Park, Sang Hyoung; Kim, Ju-Ock; Hong, Jang Hee; Seok, Jeong Ho; Lee, Choong Jae

doi:10.4046/trd.2014.76.3.120

Cited by 12 publications

(11 citation statements)

References 30 publications

(34 reference statements)

Supporting

Mentioning

Contrasting

Order By: Relevance

“…The isoflavone genistein was previously shown to inhibit pyocyanin-induced IL-8 secretion (85), likely via genistein's ability to inhibit tyrosine kinase activity (69, 86 -88). We observed induction of IL-8 after treating 16HBE or Calu-3 ALIs with 25 M pyocyanin for 24 h. Apigenin (89 -91), wogonin (91)(92)(93)(94), and tangeritin (95)(96)(97) have previously also been shown to inhibit tyrosine kinases, whereas chrysin has a less inhibitory effect (88,98). Fitting with these prior observations, pyocyanin-induced IL-8 secretion was reduced in the presence of apigenin, wogonin, and tangeritin but not chrysin ( Fig.…”

Section: C and D)supporting

confidence: 79%

Flavones modulate respiratory epithelial innate immunity: Anti-inflammatory effects and activation of the T2R14 receptor

Hariri¹,

McMahon²,

Chen³

et al. 2017

Journal of Biological Chemistry

100

176

View full text Add to dashboard Cite

Chronic rhinosinusitis has a significant impact on patient quality of life, creates billions of dollars of annual healthcare costs, and accounts for ∼20% of adult antibiotic prescriptions in the United States. Because of the rise of resistant microorganisms, there is a critical need to better understand how to stimulate and/or enhance innate immune responses as a therapeutic modality to treat respiratory infections. We recently identified bitter taste receptors (taste family type 2 receptors, or T2Rs) as important regulators of sinonasal immune responses and potentially important therapeutic targets. Here, we examined the immunomodulatory potential of flavones, a class of flavonoids previously demonstrated to have antibacterial and anti-inflammatory effects. Some flavones are also T2R agonists. We found that several flavones inhibit Muc5AC and inducible NOS up-regulation as well as cytokine release in primary and cultured airway cells in response to several inflammatory stimuli. This occurs at least partly through inhibition of protein kinase C and receptor tyrosine kinase activity. We also demonstrate that sinonasal ciliated epithelial cells express T2R14, which closely co-localizes (<7 nm) with the T2R38 isoform. Heterologously expressed T2R14 responds to multiple flavones. These flavones also activate T2R14-driven calcium signals in primary cells that activate nitric oxide production to increase ciliary beating and mucociliary clearance. polymorphisms encode functional (PAV:roline, lanine, andaline at positions 49, 262, and 296, respectively) or non-functional (AVI: lanine,aline, soleucine at positions 49, 262, and 296, respectively) T2R38. Our data demonstrate that T2R14 in sinonasal cilia is a potential therapeutic target for upper respiratory infections and that flavones may have clinical potential as topical therapeutics, particularly in T2R38 AVI/AVI individuals.

show abstract

Section: C and D)supporting

confidence: 79%

Flavones modulate respiratory epithelial innate immunity: Anti-inflammatory effects and activation of the T2R14 receptor

Hariri¹,

McMahon²,

Chen³

et al. 2017

Journal of Biological Chemistry

100

176

View full text Add to dashboard Cite

show abstract

“…Flavonoids are widely distributed secondary metabolites and currently consumed in large amounts in the daily diet with anti‐inflammatory, antilipidemic, antihyperglycemic, antiviral, hepatoprotective, gastric antiulcer, cardioprotective, neuroprotective, antioxidant, and anticancer actions (Romano et al , ). The flavonoids luteolin (Lee et al , ), apigenin, and wogonin (Kim et al , ; Sikder et al , ) were reported to significantly inhibit stimulated MUC5AC secretion, production, and gene expression at concentration ranges of 5–20 μM via regulation of the NF‐κB signaling pathway. In the present study, 7,4′‐DHF at 10 μM showed similar MUC5AC inhibitory effects via regulation of not only NF‐κB but also HDAC2 and STAT6 activation.…”

Section: Discussionmentioning

confidence: 99%

The Flavonoid 7,4′‐Dihydroxyflavone Inhibits MUC5AC Gene Expression, Production, and Secretion via Regulation of NF‐κB, STAT6, and HDAC2

Liu

Weir

Busse

et al. 2015

Phytotherapy Research

View full text Add to dashboard Cite

Mucus overproduction is a significant component of the pathophysiology of obstructive lung diseases. Currently, there are only a few medications available that inhibit mucus production. Previous studies showed that glycyrrhizin, a triterpenoid in Glycyrrhiza uralensis (G. uralensis) inhibits mucin 5AC (MUC5AC) mRNA and protein expression. Other potential mucus production inhibitory compounds contained within in G. uralensis have not been fully investigated. The aim of the present study was to determine if the G. uralensis flavonoid 7,4'-dihydroxyflavone (7,4'-DHF), inhibits MUC5AC gene expression, mucus production and secretion and if so, to elucidate the mechanism of this inhibition. 7,4'-DHF significantly decreased phorbol 12-myristate 13-acetate (PMA) stimulated NCI-H292 human airway epithelial cell MUC5AC gene expression and mucus production, at a 28 fold lower concentration than glycyrrhizin (IC50 value of 1.4µM vs 38 µM, respectively), 7,4'-DHF also inhibited MUC5AC mucus secretion. Inhibition was associated with the suppression of NF-κB, STAT6 activation and enhanced HDAC2 expression. In a murine model of asthma, 7,4'-DHF treated mice exhibited a marked reduction in MUC5AC secretion in the bronchoalveolar lavage (BAL) fluid compared with control mice. These findings, together with previous findings linking NF-κB, STAT6 and HDAC2 modulation to the control of MUC5AC expression, demonstrate that 7,4'-DHF is a newly identified component of G. uralensis that regulates MUC5AC expression and secretion via regulation of NF-κB, STAT6 and HDAC2.

show abstract

“…Flavonoids are natural compounds found in many plants and vegetables. They have been shown to possess a range of effects on biological systems . Apigenin (Figure ) belongs to the flavone subclass of flavonoids.…”

Section: Introductionmentioning

confidence: 99%

“…They have been shown to possess a range of effects on biological systems. [16,17] Apigenin (Figure 1) belongs to the flavone subclass of flavonoids. Apigenin has shown promising effects in the treatment of various cancers.…”

Section: Introductionmentioning

confidence: 99%

The antiproliferative and apoptotic effects of apigenin on glioblastoma cells

Stump

Santee

Williams

et al. 2017

Journal of Pharmacy and Pharmacology

View full text Add to dashboard Cite

Objectives Glioblastoma (GBM) is highly proliferative, infiltrative, malignant and the most deadly form of brain tumour. The epidermal growth factor receptor (EGFR) is overexpressed, amplified and mutated in GBM and has been shown to play key and important roles in the proliferation, growth and survival of this tumour. The goal of our study was to investigate the antiproliferative, apoptotic and molecular effects of apigenin in GBM. Methods Proliferation and viability tests were carried out using the trypan blue exclusion, MTT and lactate dehydrogenase (LDH) assays. Flow cytometry was used to examine the effects of apigenin on the cell cycle check-points. In addition, we determined the effects of apigenin on EGFR-mediated signalling pathways by Western blot analyses. Key findings Our results showed that apigenin reduced cell viability and proliferation in a dose-and time-dependent manner while increasing cytotoxicity in GBM cells. Treatment with apigenin-induced is poly ADP-ribose polymerase (PARP) cleavage and caused cell cycle arrest at the G2M checkpoint. Furthermore, our data revealed that apigenin inhibited EGFR-mediated phosphorylation of mitogen-activated protein kinase (MAPK), AKT and mammalian target of rapamycin (mTOR) signalling pathways and attenuated the expression of Bcl-xL. Conclusion Our results demonstrated that apigenin has potent inhibitory effects on pathways involved in GBM proliferation and survival and could potentially be used as a therapeutic agent for GBM.

show abstract

Apigenin and Wogonin Regulate Epidermal Growth Factor Receptor Signaling Pathway Involved in MUC5AC Mucin Gene Expression and Production from Cultured Airway Epithelial Cells

Cited by 12 publications

References 30 publications

Flavones modulate respiratory epithelial innate immunity: Anti-inflammatory effects and activation of the T2R14 receptor

Flavones modulate respiratory epithelial innate immunity: Anti-inflammatory effects and activation of the T2R14 receptor

The Flavonoid 7,4′‐Dihydroxyflavone Inhibits MUC5AC Gene Expression, Production, and Secretion via Regulation of NF‐κB, STAT6, and HDAC2

The antiproliferative and apoptotic effects of apigenin on glioblastoma cells

Contact Info

Product

Resources

About