Alpinia oxyphylla oil induces apoptosis of hepatocellular carcinoma cells via PI3K/Akt pathway in vitro and in vivo

Background: The anti-tumor properties of Alpinia oxyphylla Miquel (A. oxyphylla) extracts and their petroleum ether (PE) fractions have long attracted scientific attention. These extracts’ anti-tumor activity and mechanisms in vivo are still unclear. This study was designed to investigate the anti-t...

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Main Authors: Fuhai Hui, Xiaochun Qin, Qiao Zhang, Ruolan Li, Mingyue Liu, Tianshu Ren, Mingyi Zhao, Qingchun Zhao
Format: Article
Language:English
Published: Elsevier 2019-01-01
Series:Biomedicine & Pharmacotherapy
Subjects:
Online Access:http://www.sciencedirect.com/science/article/pii/S0753332218352624
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record_format Article
collection DOAJ
language English
format Article
sources DOAJ
author Fuhai Hui
Xiaochun Qin
Qiao Zhang
Ruolan Li
Mingyue Liu
Tianshu Ren
Mingyi Zhao
Qingchun Zhao
spellingShingle Fuhai Hui
Xiaochun Qin
Qiao Zhang
Ruolan Li
Mingyue Liu
Tianshu Ren
Mingyi Zhao
Qingchun Zhao
Alpinia oxyphylla oil induces apoptosis of hepatocellular carcinoma cells via PI3K/Akt pathway in vitro and in vivo
Biomedicine & Pharmacotherapy
Alpinia oxyplylla
Petroleum ether fraction
Hepatocellular carcinoma
Apoptosis
PI3K/Akt pathway
author_facet Fuhai Hui
Xiaochun Qin
Qiao Zhang
Ruolan Li
Mingyue Liu
Tianshu Ren
Mingyi Zhao
Qingchun Zhao
author_sort Fuhai Hui
title Alpinia oxyphylla oil induces apoptosis of hepatocellular carcinoma cells via PI3K/Akt pathway in vitro and in vivo
title_short Alpinia oxyphylla oil induces apoptosis of hepatocellular carcinoma cells via PI3K/Akt pathway in vitro and in vivo
title_full Alpinia oxyphylla oil induces apoptosis of hepatocellular carcinoma cells via PI3K/Akt pathway in vitro and in vivo
title_fullStr Alpinia oxyphylla oil induces apoptosis of hepatocellular carcinoma cells via PI3K/Akt pathway in vitro and in vivo
title_full_unstemmed Alpinia oxyphylla oil induces apoptosis of hepatocellular carcinoma cells via PI3K/Akt pathway in vitro and in vivo
title_sort alpinia oxyphylla oil induces apoptosis of hepatocellular carcinoma cells via pi3k/akt pathway in vitro and in vivo
publisher Elsevier
series Biomedicine & Pharmacotherapy
issn 0753-3322
publishDate 2019-01-01
description Background: The anti-tumor properties of Alpinia oxyphylla Miquel (A. oxyphylla) extracts and their petroleum ether (PE) fractions have long attracted scientific attention. These extracts’ anti-tumor activity and mechanisms in vivo are still unclear. This study was designed to investigate the anti-tumor activity and the underlying mechanism of PE’s effect on hepatocellular carcinoma (HCC) in vitro and in vivo. Materials and method: The anti-tumor activity of PE was evaluated by MTT assay and xenograft study. Mechanistic studies of PE were analyzed by Hoechst 33342 staining, Annexin V-FITC/PI double-staining assay, immunohistochemical staining and western blot assay. The toxicity of the PE treatment was verified by the levels of liver and kidney function in nude mice and the H&E staining of their liver and kidney tissues. Result: PE significantly inhibited the growth of HepG2, BEL-7402, SMMC-7721 and Hep3B cells in a concentration- and time-dependent manner. Specifically, PE inhibited the growth of Hep3B cells by inducing apoptosis. PE treatment at the doses of 0.25, 0.5 and 1 g/kg for 21 days caused a respective 35.7 percent, 49.3 percent and 58.8 percent inhibition of the tumor volume, and a 14.8 percent, 40.2 percent and 55.6 percent decrease in the tumor weight, respectively, as compared with the vehicle group in tumor-loaded mice in vivo. PE promoted the release of cytochrome c from mitochondria to cytosol in a concentration-dependent manner. The expression levels of BAX (p <  0.01), cleaved caspase-9 (p <  0.01) and cleaved caspase-3 (p <  0.05) were increased significantly in the PE-treated group at the dose of 1 g/kg; the expression level of BAX (p <  0.05) was increased significantly in the PE-treated group at the dose of 0.5 g/kg, and the expression level of Bcl-2 (p <  0.01) was decreased significantly in the PE-treated group in a concentration-dependent manner. Apoptosis was induced by PE through up-regulating the expression of PTEN, down-regulating the expression of PI3K and inhibiting the phosphorylation of Akt. The liver and kidney function of the plasma and the morphology of the liver and kidney were normal in each group. Conclusion: These findings suggested that PE exhibited anti-cancer efficacy on Hep3B cell in vitro and in vivo. The induction of apoptosis might be one mechanism that underlies PE’s ability to combat cancer by inhibiting the PI3K/Akt pathway. PE has no obvious toxicity in vivo when it exerts anti-tumor effects and has the potential to develop into an alternative anti-cancer drug for HCC treatment.
topic Alpinia oxyplylla
Petroleum ether fraction
Hepatocellular carcinoma
Apoptosis
PI3K/Akt pathway
url http://www.sciencedirect.com/science/article/pii/S0753332218352624
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spelling doaj-5ad04b19700449c8871f23f71ac531c42021-05-21T04:16:27ZengElsevierBiomedicine & Pharmacotherapy0753-33222019-01-0110923652374Alpinia oxyphylla oil induces apoptosis of hepatocellular carcinoma cells via PI3K/Akt pathway in vitro and in vivoFuhai Hui0Xiaochun Qin1Qiao Zhang2Ruolan Li3Mingyue Liu4Tianshu Ren5Mingyi Zhao6Qingchun Zhao7Department of Clinical Pharmacy, Shenyang Pharmaceutical University, Shenyang 110016, China; Department of Pharmacy, General Hospital of Shenyang Military Area Command, Shenyang 110840, ChinaDepartment of Clinical Pharmacy, Shenyang Pharmaceutical University, Shenyang 110016, ChinaResearch Center for Clinical Pharmacy, State Key Laboratory for Diagnosis and Treatment of Infectious Disease, First Affiliated Hospital, College of Medicine, Zhejiang University, Hangzhou 310003, ChinaDepartment of Clinical Pharmacy, Shenyang Pharmaceutical University, Shenyang 110016, ChinaDepartment of Clinical Pharmacy, Shenyang Pharmaceutical University, Shenyang 110016, ChinaDepartment of Pharmacy, General Hospital of Shenyang Military Area Command, Shenyang 110840, ChinaDepartment of Clinical Pharmacy, Shenyang Pharmaceutical University, Shenyang 110016, China; Corresponding authors at: Department of Clinical Pharmacy, Shenyang Pharmaceutical University, No. 103 Wenhua Road, Shenyang 110016, China.Department of Clinical Pharmacy, Shenyang Pharmaceutical University, Shenyang 110016, China; Department of Pharmacy, General Hospital of Shenyang Military Area Command, Shenyang 110840, China; Corresponding authors at: Department of Clinical Pharmacy, Shenyang Pharmaceutical University, No. 103 Wenhua Road, Shenyang 110016, China.Background: The anti-tumor properties of Alpinia oxyphylla Miquel (A. oxyphylla) extracts and their petroleum ether (PE) fractions have long attracted scientific attention. These extracts’ anti-tumor activity and mechanisms in vivo are still unclear. This study was designed to investigate the anti-tumor activity and the underlying mechanism of PE’s effect on hepatocellular carcinoma (HCC) in vitro and in vivo. Materials and method: The anti-tumor activity of PE was evaluated by MTT assay and xenograft study. Mechanistic studies of PE were analyzed by Hoechst 33342 staining, Annexin V-FITC/PI double-staining assay, immunohistochemical staining and western blot assay. The toxicity of the PE treatment was verified by the levels of liver and kidney function in nude mice and the H&E staining of their liver and kidney tissues. Result: PE significantly inhibited the growth of HepG2, BEL-7402, SMMC-7721 and Hep3B cells in a concentration- and time-dependent manner. Specifically, PE inhibited the growth of Hep3B cells by inducing apoptosis. PE treatment at the doses of 0.25, 0.5 and 1 g/kg for 21 days caused a respective 35.7 percent, 49.3 percent and 58.8 percent inhibition of the tumor volume, and a 14.8 percent, 40.2 percent and 55.6 percent decrease in the tumor weight, respectively, as compared with the vehicle group in tumor-loaded mice in vivo. PE promoted the release of cytochrome c from mitochondria to cytosol in a concentration-dependent manner. The expression levels of BAX (p <  0.01), cleaved caspase-9 (p <  0.01) and cleaved caspase-3 (p <  0.05) were increased significantly in the PE-treated group at the dose of 1 g/kg; the expression level of BAX (p <  0.05) was increased significantly in the PE-treated group at the dose of 0.5 g/kg, and the expression level of Bcl-2 (p <  0.01) was decreased significantly in the PE-treated group in a concentration-dependent manner. Apoptosis was induced by PE through up-regulating the expression of PTEN, down-regulating the expression of PI3K and inhibiting the phosphorylation of Akt. The liver and kidney function of the plasma and the morphology of the liver and kidney were normal in each group. Conclusion: These findings suggested that PE exhibited anti-cancer efficacy on Hep3B cell in vitro and in vivo. The induction of apoptosis might be one mechanism that underlies PE’s ability to combat cancer by inhibiting the PI3K/Akt pathway. PE has no obvious toxicity in vivo when it exerts anti-tumor effects and has the potential to develop into an alternative anti-cancer drug for HCC treatment.http://www.sciencedirect.com/science/article/pii/S0753332218352624Alpinia oxyplyllaPetroleum ether fractionHepatocellular carcinomaApoptosisPI3K/Akt pathway