Amantadine inhibits cellular proliferation and induces the apoptosis of hepatocellular cancer cells in vitro

  • Authors:
    • Zengmei Lan
    • Zhaoyang Chong
    • Cong Liu
    • Danyang Feng
    • Dihai Fang
    • Weijin Zang
    • Jun Zhou
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  • Published online on: July 20, 2015     https://doi.org/10.3892/ijmm.2015.2289
  • Pages: 904-910
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Abstract

Hepatocellular carcinoma (HCC) is one of the most aggressive malignancies worldwide, and its incidence associated with viral infection has increased in recent years. Amantadine is a tricyclic symmetric amine that can effectively protect against the hepatitis C virus. However, its antitumor properties remain unclear. In the present study, the effects of amantadine on tumor cell viability, cell cycle regulation and apoptosis were investigated. The growth of HepG2 and SMMC‑7721 cells (HCC cell lines) was detected by an MTT assay. Flow cytometry was used to investigate cell cycle regulation and apoptosis. Reverse transcription‑quantitative polymerase chain reaction and western blot analysis were also performed to examine the expression of cell cycle‑ and apoptosis‑related genes and proteins, including cyclin E, cyclin D1, cyclin‑dependent kinase 2 (CDK2), B‑cell lymphoma 2 (Bcl‑2) and Bax. Our results demonstrated that amantadine markedly inhibited the proliferation of HepG2 and SMMC‑7721 cells in a dose‑ and time‑dependent manner and arrested the cell cycle at the G0/G1 phase. The levels of the cell cycle‑related genes and proteins (cyclin D1, cyclin E and CDK2) were reduced by amantadine, and apoptosis was significantly induced. Amantadine treatment also reduced Bcl‑2 and increased the Bax protein and mRNA levels. Additionally, Bcl‑2/Bax ratios were lower in the two HCC cell lines following amantadine treatment. Collectively, these results emphasize the role of amantadine in suppressing proliferation and inducing apoptosis in HCC cells, advocating its use as a novel tumor-suppressive therapeutic candidate.
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September-2015
Volume 36 Issue 3

Print ISSN: 1107-3756
Online ISSN:1791-244X

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Spandidos Publications style
Lan Z, Chong Z, Liu C, Feng D, Fang D, Zang W and Zhou J: Amantadine inhibits cellular proliferation and induces the apoptosis of hepatocellular cancer cells in vitro. Int J Mol Med 36: 904-910, 2015.
APA
Lan, Z., Chong, Z., Liu, C., Feng, D., Fang, D., Zang, W., & Zhou, J. (2015). Amantadine inhibits cellular proliferation and induces the apoptosis of hepatocellular cancer cells in vitro. International Journal of Molecular Medicine, 36, 904-910. https://doi.org/10.3892/ijmm.2015.2289
MLA
Lan, Z., Chong, Z., Liu, C., Feng, D., Fang, D., Zang, W., Zhou, J."Amantadine inhibits cellular proliferation and induces the apoptosis of hepatocellular cancer cells in vitro". International Journal of Molecular Medicine 36.3 (2015): 904-910.
Chicago
Lan, Z., Chong, Z., Liu, C., Feng, D., Fang, D., Zang, W., Zhou, J."Amantadine inhibits cellular proliferation and induces the apoptosis of hepatocellular cancer cells in vitro". International Journal of Molecular Medicine 36, no. 3 (2015): 904-910. https://doi.org/10.3892/ijmm.2015.2289