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Endocrine, Metabolic & Immune Disorders - Drug Targets

Editor-in-Chief

ISSN (Print): 1871-5303
ISSN (Online): 2212-3873

Research Article

Curcumin Suppresses Epithelial Growth Factor Receptor (EGFR) and Proliferative Protein (Ki 67) in Acute Lung Injury and Lung Fibrosis In vitro and In vivo

Author(s): Sadiya Bi Shaikh, Ashwini Prabhu and Yashodhar Prabhakar Bhandary*

Volume 20, Issue 4, 2020

Page: [558 - 563] Pages: 6

DOI: 10.2174/1871530319666190823160230

Price: $65

Abstract

Background: Acute lung injury is one of the common conditions caused due to bleomycin therapy which leads to pulmonary fibrosis, which is one of the severe interstitial lung diseases most commonly affecting the elderly individuals. EGFR and Ki67 can be marked as beneficial markers for detecting pulmonary fibrosis based on which clinicians can guide the therapy.

Objective: The aim of the study was to evaluate the effect of curcumin as an intervention on two prognostic markers EGFR and Ki67 in bleomycin-induced basal alveolar epithelial cells and C57BL/6 mice. Protein expressions and pathological expressions of EGFR and Ki67 were evaluated to analyze the effect of curcumin via both in vitro and in vivo approaches.

Methods: The effect of curcumin was investigated both on cell lines (A549) and animal model (both normal and bleomycin-induced mice, n=6) via techniques like western blotting for protein expression. Techniques like immunofluorescence and immunohistochemistry were carried out and examined under confocal microscopy and phase contrast microscopy to analyze the expressions of the said biomarkers. Bleomycin was used as a causative agent to induce inflammation.

Results: The natural polyphenol curcumin could downregulate the expressions levels of Ki67 and EGFR both in vitro and in vivo. Immunofluorescence analysis of proliferative marker Ki67 showed a reduced expression on curcumin treatment in vitro. The pathological sections from treated lungs showed a significant decrease in EGFR and Ki67 levels when exposed to curcumin.

Conclusion: We conclude that curcumin, a well-known natural bioactive compound holds strong antiproliferative effects on Ki67 and EGFR expressions.We observed that a clinical outcome in the diagnosis of pulmonary fibrosis remains to be unconvincing so far. Curcumin can be considered as a potential therapeutic.

Keywords: Acute lung injury, pulmonary fibrosis, bleomycin, curcumin, Ki67, EGFR.

Graphical Abstract

[1]
Gouda, M.M.; Prabhu, A.; Bhandary, Y.P. Curcumin alleviates IL-17A-mediated p53-PAI-1 expression in bleomycin-induced alveolar basal epithelial cells. J. Cell. Biochem., 2018, 119(2), 2222-2230.
[http://dx.doi.org/10.1002/jcb.26384] [PMID: 28902433]
[2]
Adegunsoye, A.; Vij, R.; Noth, I. Integrating Genomics Into Management of Fibrotic Interstitial Lung Disease. Chest, 2019, 155(5), 1026-1040.
[http://dx.doi.org/10.1016/j.chest.2018.12.011] [PMID: 30660786]
[3]
Jo, H.E.; Randhawa, S.; Corte, T.J.; Moodley, Y. Idiopathic pulmonary fibrosis and the elderly: diagnosis and management considerations. Drugs Aging, 2016, 33(5), 321-334.
[http://dx.doi.org/10.1007/s40266-016-0366-1] [PMID: 27083934]
[4]
King, C.S.; Aryal, S.; Nathan, S.D. Idiopathic Pulmonary Fibrosis: Phenotypes and Comorbidities; Idiopathic Pulmonary Fibrosis Humana Press: Cham, 2019, pp. 273-297.
[http://dx.doi.org/10.1007/978-3-319-99975-3_11]
[5]
Zhang, A.Y.; Chiam, K.; Haupt, Y.; Fox, S.; Birch, S.; Tilley, W.; Butler, L.M.; Knudsen, K.; Comstock, C.; Rasiah, K.; Grogan, J.; Mahon, K.L.; Bianco-Miotto, T.; Ricciardelli, C.; Böhm, M.; Henshall, S.; Delprado, W.; Stricker, P.; Horvath, L.G.; Kench, J.G. An analysis of a multiple biomarker panel to better predict prostate cancer metastasis after radical prostatectomy. Int. J. Cancer, 2019, 144(5), 1151-1159.
[http://dx.doi.org/10.1002/ijc.31906] [PMID: 30288742]
[6]
Chirieac, L.R. Ki-67 expression in pulmonary tumors. Transl. Lung Cancer Res., 2016, 5(5), 547-551.
[http://dx.doi.org/10.21037/tlcr.2016.10.13] [PMID: 27827465]
[7]
Martinelli, M.; Pacilli, AM.; Rivetti, S.; Lauriola, M.; Fasano, L.; Carbonara, P.; Mattei, G.; Valentini, I.; Scapoli, L.; Solmi, R. A role for epidermal growth factor receptor in idiopathic pulmonary fibrosis onset, 2011.
[http://dx.doi.org/10.1007/s11033-010-0594-0]
[8]
Niemiec, J.; Kolodziejski, L.; Dyczek, S. EGFR LI and Ki-67 LI are independent prognostic parameters influencing survivals of surgically treated squamous cell lung cancer patients. Neoplasma, 2005, 52(3), 231-237.
[PMID: 15875085]
[9]
Smargiassi, A.; Pasciuto, G.; Conte, E.G.; Andreani, M.; Marra, R.; Richeldi, L. Pharmacologic Treatment of IPF; Idiopathic Pulmonary Fibrosis Humana Press: Cham, 2019, pp. 325-364.
[10]
Gouda, M.M.; Prabhu, A.; Bhandary, Y.P. IL-17A suppresses and curcumin up-regulates Akt expression upon bleomycin exposure. Mol. Biol. Rep., 2018, 45(4), 645-650.
[http://dx.doi.org/10.1007/s11033-018-4199-3] [PMID: 29808357]
[11]
Ortega, A.M.; Campos, M.R. Bioactive Compounds as Therapeutic Alternatives.Bioactive Compounds; Woodhead Publishing, 2019, pp. 247-264.
[http://dx.doi.org/10.1016/B978-0-12-814774-0.00013-X]
[12]
Taylor, C.R. Introduction to Predictive Biomarkers: Definitions and Characteristics. In: Predictive Biomarkers in Oncology Springer, Cham; , 2019; pp. 3-18.
[13]
Vallath, S.; Hynds, R.E.; Succony, L.; Janes, S.M.; Giangreco, A. Targeting EGFR signalling in chronic lung disease: therapeutic challenges and opportunities. Eur. Resp. J., 2014, 44(2), 513-522.
[14]
Y.u, X.; Zhao, X.; Zhang, J.; Li, Y.; Sheng, P.; Ma, C.; Zhang, L.; Hao, X.; Zheng, X.; Xing, Y.; Qiao, H. Dacomitinib, a new pan-EGFR inhibitor, is effective in attenuating pulmonary vascular remodeling and pulmonary hypertension. Eur. J. Pharmacol., 2019, 850, 97-108.
[http://dx.doi.org/10.1016/j.ejphar.2019.02.008]
[15]
Menon, S.S.; Guruvayoorappan, C.; Sakthivel, K.M.; Rasmi, R.R. Ki-67 protein as a tumour proliferation marker. Clin. Chim. Acta, 2019, 491, 39-45.
[http://dx.doi.org/10.1016/j.cca.2019.01.011] [PMID: 30653951]
[16]
Kim, S.Y.; Myung, J.K.; Kim, H.R.; Na, I.I.; Koh, J.S.; Baek, H.J.; Kim, C.H. Factors that Predict Clinical Benefit of EGFR TKI Therapy in Patients with EGFR Wild-Type Lung Adenocarcinoma. Tuberc. Respir. Dis. (Seoul), 2019, 82(1), 62-70.
[http://dx.doi.org/10.4046/trd.2018.0004] [PMID: 29926551]
[17]
Gouda, M.M.; Bhandary, Y.P. Curcumin down-regulates IL-17A mediated p53-fibrinolytic system in bleomycin induced acute lung injury in vivo. J. Cell. Biochem., 2018, 119(9), 7285-7299.
[http://dx.doi.org/10.1002/jcb.27026] [PMID: 29775223]

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