Novel angiotensin receptor blocker, azilsartan induces oxidative stress and NFkB-mediated apoptosis in hepatocellular carcinoma cell line HepG2

  • Biomed Pharmacother. 2018 Mar;99:939-946. doi: 10.1016/j.biopha.2018.01.117.
Elham Ahmadian  1 ,  Ahmad Yari Khosroushahi  2 ,  Aziz Eftekhari  3 ,  Safar Farajnia  4 ,  Hossein Babaei  5 ,  Mohammad Ali Eghbal  6
Affiliations
  • 1. Drug Applied Research Center, Tabriz University of Medical Sciences, Tabriz, Iran; Pharmacology and Toxicology Department, Maragheh University of Medical Sciences, Maragheh, Iran; Students' Research Committee, Tabriz University of Medical Sciences, Tabriz, Iran; Department of Basic Sciences, Maragheh University of Medical Sciences, Maragheh, Iran. Electronic address: [email protected].
  • 2. Department of Pharmacognosy, Faculty of Pharmacy, Tabriz University of Medical Sciences, Tabriz, Iran. Electronic address: [email protected].
  • 3. Pharmacology and Toxicology Department, Maragheh University of Medical Sciences, Maragheh, Iran; Department of Basic Sciences, Maragheh University of Medical Sciences, Maragheh, Iran; Toxicology Research Center, Maragheh University of Medical Sciences, Maragheh, Iran. Electronic address: [email protected].
  • 4. Drug Applied Research Center, Tabriz University of Medical Sciences, Tabriz, Iran. Electronic address: [email protected].
  • 5. Drug Applied Research Center, Tabriz University of Medical Sciences, Tabriz, Iran; Department of Pharmaclogy and Toxicology, Faculty of Pharmacy, Tabriz University of Medical Sciences, Tabriz, Iran. Electronic address: [email protected].
  • 6. Drug Applied Research Center, Tabriz University of Medical Sciences, Tabriz, Iran; Department of Pharmaclogy and Toxicology, Faculty of Pharmacy, Tabriz University of Medical Sciences, Tabriz, Iran; Biotechnology Research Center, Tabriz University of Medical Sciences, Tabriz, Iran. Electronic address: [email protected].
PMID: 29710494 DOI: 10.1016/j.biopha.2018.01.117
Abstract

Overexpression of Renin angiotensin system (Ras) components and nuclear factor-kappa B (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 Bay 11-7082 (as NF-kB inhibitor). HepG2 cells were treated with different concentrations of azilsartan and Bay 11-7082. 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. The cytotoxic effects of different concentration of azilsartan and Bay11- 7082 on HepG2 cells were observed as a reduction in cell viability, increased 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. These findings suggest that azilsartan and Bay11- 7082 in combination or alone have strong potential as an agent for prevention or treatment of liver Cancer after further studies.

Keywords
Angiotensin; Apoptosis; Azilsartan; Liver cancer; NF-kB pathway.
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