title: Amantadine inhibits cellular proliferation and induces the apoptosis of hepatocellular cancer cells in vitro.
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.
authors.affiliation: Department of Pharmacology, Xi'an Jiaotong University Health Science Center, Xi'an, Shaanxi 710061, P.R. China.
authors.forename: Zengmei
authors.initials: Z
authors.lastname: Lan
authors.affiliation: Department of Pharmacology, Xi'an Jiaotong University Health Science Center, Xi'an, Shaanxi 710061, P.R. China.
authors.forename: Zhaoyang
authors.initials: Z
authors.lastname: Chong
authors.affiliation: Department of Pharmacology, Xi'an Jiaotong University Health Science Center, Xi'an, Shaanxi 710061, P.R. China.
authors.forename: Cong
authors.initials: C
authors.lastname: Liu
authors.affiliation: Department of Pharmacology, Xi'an Jiaotong University Health Science Center, Xi'an, Shaanxi 710061, P.R. China.
authors.forename: Danyang
authors.initials: D
authors.lastname: Feng
authors.affiliation: Department of Cardiology, Xi'an Jiaotong University Health Science Center, Xi'an, Shaanxi 710061, P.R. China.
authors.forename: Dihai
authors.initials: D
authors.lastname: Fang
authors.affiliation: Department of Pharmacology, Xi'an Jiaotong University Health Science Center, Xi'an, Shaanxi 710061, P.R. China.
authors.forename: Weijin
authors.initials: W
authors.lastname: Zang
authors.affiliation: Department of Pharmacology, Xi'an Jiaotong University Health Science Center, Xi'an, Shaanxi 710061, P.R. China.
authors.forename: Jun
authors.initials: J
authors.lastname: Zhou
mesh_terms: D000547:Amantadine / Q000494:pharmacology*; D000970:Antineoplastic Agents / Q000494:pharmacology; D000998:Antiviral Agents / Q000494:pharmacology*; D017209:Apoptosis / Q000187:drug effects*; D006528:Carcinoma, Hepatocellular / Q000188:drug therapy* / Q000235:genetics / Q000473:pathology; D002453:Cell Cycle / Q000187:drug effects; D045744:Cell Line, Tumor; D049109:Cell Proliferation / Q000187:drug effects*; D015972:Gene Expression Regulation, Neoplastic / Q000187:drug effects; D006801:Humans; D008099:Liver / Q000187:drug effects* / Q000378:metabolism / Q000473:pathology; D008113:Liver Neoplasms / Q000188:drug therapy* / Q000235:genetics / Q000473:pathology
chemical_list: D000970:Antineoplastic Agents; D000998:Antiviral Agents; D000547:Amantadine