Natural product pectolinarigenin inhibits proliferation, induces apoptosis, and causes G2/M phase arrest of HCC via PI3K/AKT/mTOR/ERK signaling pathway
Authors Wu T, Dong X, Yu D, Shen Z, Yu J, Yan S
Received 2 September 2018
Accepted for publication 6 November 2018
Published 3 December 2018 Volume 2018:11 Pages 8633—8642
Checked for plagiarism Yes
Review by Single anonymous peer review
Peer reviewer comments 3
Editor who approved publication: Dr Carlos E Vigil
Tianchun Wu,1–3 Xiaogang Dong,4 Dongdong Yu,1–3 Zhenhua Shen,1–3 Jinbei Yu,5 Sheng Yan1–3
1Division of Hepatobiliary and Pancreatic Surgery, Department of Surgery, First Affiliated Hospital, School of Medicine, Zhejiang University, Hangzhou, People’s Republic of China; 2Key Laboratory of Precision Diagnosis and Treatment for Hepatobiliary and Pancreatic Tumor of Zhejiang Province, Hangzhou, People’s Republic of China; 3State Key Laboratory & Collaborative Innovation Center for Diagnosis and Treatment of Infectious Diseases, First Affiliated Hospital, Zhejiang University School of Medicine, Hangzhou, People’s Republic of China; 4Division of Hepatobiliary and Pancreatic Surgery, Department of Surgery, Affiliated Tumor Hospital of Xinjiang Medical University, Urumqi, Xinjiang Uygur Autonomous Region, People’s Republic of China; 5Department of Neurology, the First Affiliated Hospital of Zhengzhou University, Zhengzhou, People’s Republic of China
Background: Hepatocellular carcinoma (HCC) is characterized by considerable phenotypic and molecular heterogeneity, but the overall survival of HCC patients remains extremely poor. Thus, novel and efficient alternatives to antitumor agents are urgently needed. Pectolinarigenin, a flavonoid compound extract, has been previously reported for the treatment of nasopharyngeal cancer. However, the potential antitumor roles of pectolinarigenin in HCC have not been clearly elaborated. In the present study, we investigated its role in HCC treatment and explored the potential molecular mechanism(s).
Materials and methods: HCC cell lines SMMC7721 and PLC5 were cultured and treated with indicated concentrations of pectolinarigenin. For the HCC cell proliferation, after HCC cells were stimulated with indicated concentrations of pectolinarigenin, the cell viability was detected in CCK-8 and colony-forming assays. HCC cell invasion/migration assay was performed by Transwell and wound scratch methods. Additionally, cellular apoptosis and cell cycle arrest analysis was performed with flow cytometric analysis. Finally, the involved underlying signaling pathway, the PI3K/AKT/mTOR/ERK signaling-related molecular markers were detected through Western blot methods with indicated antibodies. Meanwhile, antitumor activity of pectolinarigenin was also assessed in tumor-bearing mice.
Results: The results indicated that the treatment with pectolinarigenin significantly inhibited cell proliferation and migratory and invasive abilities of SMMC7721 and PLC5 cells in concentration- and time-dependent manner. Meanwhile, pectolinarigenin markedly induced cell apoptosis and G2/M phase arrest in SMMC7721 and PLC5 cells, which was associated with apoptosis- and cell cycle-related protein levels, respectively. Furthermore, pectolinarigenin inhibited PI3K/AKT/mTOR/ERK signaling pathway. It also significantly suppressed HCC tumor growth in vivo.
Conclusion: Pectolinarigenin could suppress the viability and motility and cause apoptosis and G2/M phase arrest in HCC cell lines by inhibiting the PI3K/AKT/mTOR/ERK signaling pathway. This might be an appealing potential therapeutic agent for HCC treatment.
Keywords: hepatocellular carcinoma, pectolinarigenin, apoptosis, cell cycle arrest, antitumor
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