Adv Pharm Bull. 2020;10(1): 65-71.
doi: 10.15171/apb.2020.008
PMID: 32002363
PMCID: PMC6983989
Scopus ID: 85076900976
  Abstract View: 527
  PDF Download: 336

Research Article

Alpha7 Nicotinic Acetylcholine Receptor Mediates Nicotine-induced Apoptosis and Cell Cycle Arrest of Hepatocellular Carcinoma HepG2 Cells

Khalil Hajiasgharzadeh 1 ORCID logo, Mohammad Hossein Somi 2 ORCID logo, Behzad Mansoori 1 ORCID logo, Mohammad Amin Doustvandi 1 ORCID logo, Fatemeh Vahidian 1, Mohsen Alizadeh 1, Ahad Mokhtarzadeh 1 ORCID logo, Dariush Shanehbandi 1 ORCID logo, Behzad Baradaran 1,3* ORCID logo

1 Immunology Research Center, Tabriz University of Medical Sciences, Tabriz, Iran.
2 Liver and Gastrointestinal Diseases Research Center, Tabriz University of Medical Sciences, Tabriz, Iran.
3 Department of Immunology, Faculty of Medicine, Tabriz University of Medical Sciences, Tabriz, Iran.


Purpose: The cytotoxic properties upon treatment with nicotine have been reported in several studies, but the underlying mechanisms remain not fully defined. The alpha7 nicotinic acetylcholine receptor (α7nAChR) is one of the important nicotinic receptors, which nicotine partly by binding to this receptor exerts its effects. The current study aimed to investigates the influences of nicotine on cellular proliferative and apoptotic activities and tried to determine the involvement of α7nAChR in these functions.

Methods: Human hepatocellular carcinoma (HepG2) cell line was used to determine the individual or combined effects of treatments with nicotine (10 μM) and specific siRNA (100 nM) targeting α7nAChR expression. The MTT assay, DAPI staining assay, and flow cytometry assay were applied to measure the cell viability, apoptosis and cell cycle progression of the cells, respectively. In addition, the changes in the mRNA level of the genes were assessed by qRT-PCR.

Results: Compared to control groups, the cells treated with nicotine exhibited significant dosedependent decreases in cell viability (log IC50 = -5.12±0.15). Furthermore, nicotine induced apoptosis and cell cycle arrest especially at G2/M Phase. The qRT-PCR revealed that nicotine increased the mRNA levels of α7nAChR as well as caspase-3 and suppressed the expression of cyclin B1. Treatment with α7-siRNA abolished these effects of nicotine.

Conclusion: These experiments determined that upregulation of α7nAChR by nicotine inhibits HepG2 cells proliferation and induces their apoptosis. These effects blocked by treatment with α7-siRNA, which indicates the involvement of α7nAChR pathways in these processes.

Keywords: Alpha7 nicotinic acetylcholine receptor, Small interfering RNA, Nicotine, HepG2, Apoptosis
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Submitted: 22 May 2019
Revision: 01 Aug 2019
Accepted: 13 Aug 2019
ePublished: 11 Dec 2019
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