The prophylactic effect of azilsartan and Bay11-7082 on hepatocellular carcinoma cell line HepG2 proliferation

ElhamAhmadiana,b,c,e,, Aziz Eftekhari c,d, Mohammad Ali Eghbala,b,c*

aDrug Applied Research Center, Tabriz University of Medical Sciences, Tabriz, Iran

bBiotechnology Research Center, Tabriz University of Medical Sciences, Tabriz, Iran

cPharmacology and Toxicology Department, School of Pharmacy, Tabriz University of Medical Sciences, Tabriz, Iran

dStudents’ Research Committee, Tabriz University of Medical Sciences, Tabriz, Iran

Abstract (300 word limit)

Statement of the Problem:Over expression of renin angiotensin system (RAS) and nuclear factor-kappaB (NF-kB) has a key role in various cancers. Blockade of RAS and NF-kB pathway has been suggested to reduce cancer cell proliferation. This study aimed to investigate the role of angiotensin II and NF-kB pathway in liver hepatocellular carcinoma cell line (HepG2) proliferation by using azilsartan (as a novel Ag II antagonist) and Bay11-7082 (as NF-kB inhibitor).

Methodology & Theoretical Orientation:HepG2 cells were treated with different concentrations of azilsartan and Bay11-7082. Cytotoxicity was determined after 24, 48, and 72 h by MTT assay. Reactive oxygen spices (ROS) generation and cytochrome c release were measured following azilsartan and Bay11- 7082 treatment. Apoptosis was analyzed qualitatively by DAPI staining and quantitatively through flow cytometry methodologies and Bax and Bcl-2 mRNA and protein levels were assessed by real time PCR and ELISA methods, respectively.

Findings:The cytotoxic effects of different concentration of azilsartan and Bay11- 7082 on HepG2 cells were observed as a reduction in cell viability, ROS formation, cytochrome c release and apoptosis induction. These effects were found to correlate with a shift in Bax level and a downward trend in the expression of Bcl-2.

Conclusion & Significance:These findings suggest that azilsartan and Bay11- 7082 in combination or alone have strong potential for development as an agent for prevention against liver cancer after further studies.

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Recent Publications (minimum 5)

1.Tamaddonfard E, Farshid AA, Ahmadian E, Hamidhoseyni A. Crocin enhanced functional recovery after sciatic nerve crush injury in rats. Iranian journal of basic medical sciences. 2013 Jan 13;16(1):83-90.

2.Ahmadian E, Pennefather PS, Eftekhari A, Heidari R, Eghbal MA. Role of renin-angiotensin system in liver diseases: an outline on the potential therapeutic points of intervention. Expert Review of Gastroenterology & Hepatology. 2016 Nov 1;10(11):1279-88.

3.Ahmadian E, Eftekhari A, Fard JK, Babaei H, Nayebi AM, Mohammadnejad D, Eghbal MA. In vitro and in vivo evaluation of the mechanisms of citalopram-induced hepatotoxicity. Archives of pharmacal research. 2016 Jun 6:1-8.

4.Jafari S, Ahmadian E, Fard JK, Khosroushahi AY. Biomacromolecule based nanoscaffolds for cell therapy. Journal of Drug Delivery Science and Technology. 2016 Nov 29.

5.Ahmadian E, Babaei H, Nayebi AM, Eftekhari A, Eghbal MA. Venlafaxine-Induced Cytotoxicity Towards Isolated Rat Hepatocytes Involves Oxidative Stress and Mitochondrial/Lysosomal Dysfunction.

6.Eftekhari A, Saeedi A, Mandegary A, Ahmadian E, Mohammadi H. TGF 1 codon-10 and codon-25 polymorphisms influence the spirometry parameters in the workers of sweet-and sour-gas refinery plants. Toxicology Letters. 2014(229):S94.

7.Ahmadian E, Pennefather PS, Eftekhari A, Heidari R, Eghbal MA. Role of renin-angiotensin system in liver diseases: an outline on the potential therapeutic points of intervention. Expert Review of Gastroenterology & Hepatology. 2016 Nov 1;10(11):1279-88.

8.Eghbal MA, Eftekhari A, Ahmadian E, Azarmi Y, Parvizpur A. A Review of Biological and Pharmacological Actions of Melatonin: Oxidant and Prooxidant Properties. J Pharma Reports. 2016;1(106):2.

9.Ahmadian E, Jafari S, Khosroushahi AY. Role of angiotensin II in stem cell therapy of cardiac disease. Journal of Renin-Angiotensin-Aldosterone System. 2015 Dec 15:1470320315621225.

Biography (150 word limit)

I have experience in evaluating the cytotoxic mechanisms of different drugs/xenobiotics in different cell lines and also in vivo. In particular evaluating the possible cytotoxic action of the blockers of renin angiotensin system in various cell lines has proved pleiotropic effects of this drugs apart from their antihypertensive properties. I have research background on investigating the plausible anti cancer effect of these drug classes. Also I am interested in searching the effects of renin angiotensin system in the function of stem cells.

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Full name: ElhamAhmadian
Contact number:+989144454094
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Category: (Oral presentation/ Poster presentation): oral

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