Veratramine suppresses human HepG2 liver cancer cell growth in vitro and in vivo by inducing autophagic cell death

Yin,Linlin; Xia,Yonghui; Xu,Ping; Zheng,Wenli; Gao,Yuanyuan; Xie,Faqin; Ji,Zhaoning

doi:10.3892/or.2020.7622

Veratramine suppresses human HepG2 liver cancer cell growth in vitro and in vivo by inducing autophagic cell death

Authors:
- Linlin Yin
- Yonghui Xia
- Ping Xu
- Wenli Zheng
- Yuanyuan Gao
- Faqin Xie
- Zhaoning Ji
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Affiliations: Department of Oncology, Yijishan Hospital of Wannan Medical College, Wuhu, Anhui 241001, P.R. China, Department of Respiratory Medicine, The Second Affiliated Hospital of Wannan Medical College, Wuhu, Anhui 241001, P.R. China
Published online on: May 25, 2020 https://doi.org/10.3892/or.2020.7622
Pages: 477-486
Copyright: © Yin et al. This is an open access article distributed under the terms of Creative Commons Attribution License.

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Abstract

Liver cancer is the second leading cause of cancer‑related deaths. Traditional therapeutic strategies, such as chemotherapy, targeted therapy and interventional therapy, are inefficient and are accompanied by severe side effects for patients with advanced liver cancer. Therefore, it is crucial to develop a safer more effective drug to treat liver cancer. Veratramine, a known natural steroidal alkaloid derived from plants of the lily family, exerts anticancer activity in vitro. However, the underlying mechanism and whether it has an antitumor effect in vivo remain unknown. In the present study, the data revealed that veratramine significantly inhibited HepG2 cell proliferation, migration and invasion in vitro. Moreover, it was revealed that veratramine induced autophagy‑mediated apoptosis by inhibiting the PI3K/Akt/mTOR signaling pathway, which partly explained the underlying mechanism behind its antitumor activity. Notably, the results of in vivo experiments also revealed that veratramine treatment (2 mg/kg, 3 times a week for 4 weeks) significantly inhibited subcutaneous tumor growth of liver cancer cells, with a low systemic toxicity. Collectively, the results of the present study indicated that veratramine efficiently suppressed liver cancer HepG2 cell growth in vitro and in vivo by blocking the PI3K/Akt/mTOR signaling pathway to induce autophagic cell death. Veratramine could be a potential therapeutic agent for the treatment of liver cancer.

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