Enhancing the Anticancer Activity of Antrodia cinnamomea in Hepatocellular Carcinoma Cells via Cocultivation With Ginger: The Impact on Cancer Cell Survival Pathways
Antrodia cinnamomea (AC) is a medicinal fungal species that has been widely used traditionally in Taiwan for the treatment of diverse health-related conditions including cancer. It possesses potent anti-inflammatory and antioxidant properties in addition to its ability to promote cancer cell death i...
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doaj-9c289955c11e46b489f9026c0c9145f92020-11-24T22:25:47ZengFrontiers Media S.A.Frontiers in Pharmacology1663-98122018-07-01910.3389/fphar.2018.00780330604Enhancing the Anticancer Activity of Antrodia cinnamomea in Hepatocellular Carcinoma Cells via Cocultivation With Ginger: The Impact on Cancer Cell Survival PathwaysSan-Yuan Chen0San-Yuan Chen1Ying-Ray Lee2Ming-Chia Hsieh3Hany A. Omar4Hany A. Omar5Yen-Ni Teng6Ching-Yen Lin7Jui-Hsiang Hung8Jui-Hsiang Hung9Department of Chinese Medicine, Ditmanson Medical Foundation Chia-Yi Christian Hospital, Chiayi, TaiwanInstitute of Molecular Biology, National Chung Cheng University, Chiayi, TaiwanDepartment of Medical Research, Ditmanson Medical Foundation Chia-Yi Christian Hospital, Chiayi, TaiwanDepartment of Internal Medicine, Changhua Christian Hospital, Changhua, TaiwanSharjah Institute for Medical Research and College of Pharmacy, University of Sharjah, Sharjah, United Arab EmiratesDepartment of Pharmacology, Faculty of Pharmacy, Beni-Suef University, Beni Suef, EgyptDepartment of Biological Sciences and Technology, National University of Tainan, Tainan, TaiwanDepartment of Medical Research, Ditmanson Medical Foundation Chia-Yi Christian Hospital, Chiayi, TaiwanDrug Discovery and Development Center, Chia Nan University of Pharmacy and Science, Tainan, TaiwanDepartment of Biotechnology, Chia Nan University of Pharmacy and Science, Tainan, TaiwanAntrodia cinnamomea (AC) is a medicinal fungal species that has been widely used traditionally in Taiwan for the treatment of diverse health-related conditions including cancer. It possesses potent anti-inflammatory and antioxidant properties in addition to its ability to promote cancer cell death in several human tumors. Our aim was to improve the anticancer activity of AC in hepatocellular carcinoma (HCC) through its cocultivation with ginger aiming at tuning the active ingredients. HCC cell lines, Huh-7 and HepG2 were used to study the in vitro anticancer activity of the ethanolic extracts of AC (EAC) alone or after the cocultivation in presence of ginger (EACG). The results indicated that the cocultivation of AC with ginger significantly induced the production of important triterpenoids and EACG was significantly more potent than EAC in targeting HCC cell lines. EACG effectively inhibited cancer cells growth via the induction of cell cycle arrest at G2/M phase and induction of apoptosis in Huh-7 and HepG2 cells as indicated by MTT assay, cell cycle analysis, Annexin V assay, and the activation of caspase-3. In addition, EACG modulated cyclin proteins expression and mitogen-activated protein kinase (MAPK) signaling pathways in favor of the inhibition of cancer cell survival. Taken together, the current study highlights an evidence that EACG is superior to EAC in targeting cancer cell survival and inducing apoptotic cell death in HCC. These findings support that EACG formula can serve as a potential candidate for HCC adjuvant therapy.https://www.frontiersin.org/article/10.3389/fphar.2018.00780/fullAntrodia cinnamomeagingerhepatocellular carcinomaapoptosiscell cycleMAPK |
collection |
DOAJ |
language |
English |
format |
Article |
sources |
DOAJ |
author |
San-Yuan Chen San-Yuan Chen Ying-Ray Lee Ming-Chia Hsieh Hany A. Omar Hany A. Omar Yen-Ni Teng Ching-Yen Lin Jui-Hsiang Hung Jui-Hsiang Hung |
spellingShingle |
San-Yuan Chen San-Yuan Chen Ying-Ray Lee Ming-Chia Hsieh Hany A. Omar Hany A. Omar Yen-Ni Teng Ching-Yen Lin Jui-Hsiang Hung Jui-Hsiang Hung Enhancing the Anticancer Activity of Antrodia cinnamomea in Hepatocellular Carcinoma Cells via Cocultivation With Ginger: The Impact on Cancer Cell Survival Pathways Frontiers in Pharmacology Antrodia cinnamomea ginger hepatocellular carcinoma apoptosis cell cycle MAPK |
author_facet |
San-Yuan Chen San-Yuan Chen Ying-Ray Lee Ming-Chia Hsieh Hany A. Omar Hany A. Omar Yen-Ni Teng Ching-Yen Lin Jui-Hsiang Hung Jui-Hsiang Hung |
author_sort |
San-Yuan Chen |
title |
Enhancing the Anticancer Activity of Antrodia cinnamomea in Hepatocellular Carcinoma Cells via Cocultivation With Ginger: The Impact on Cancer Cell Survival Pathways |
title_short |
Enhancing the Anticancer Activity of Antrodia cinnamomea in Hepatocellular Carcinoma Cells via Cocultivation With Ginger: The Impact on Cancer Cell Survival Pathways |
title_full |
Enhancing the Anticancer Activity of Antrodia cinnamomea in Hepatocellular Carcinoma Cells via Cocultivation With Ginger: The Impact on Cancer Cell Survival Pathways |
title_fullStr |
Enhancing the Anticancer Activity of Antrodia cinnamomea in Hepatocellular Carcinoma Cells via Cocultivation With Ginger: The Impact on Cancer Cell Survival Pathways |
title_full_unstemmed |
Enhancing the Anticancer Activity of Antrodia cinnamomea in Hepatocellular Carcinoma Cells via Cocultivation With Ginger: The Impact on Cancer Cell Survival Pathways |
title_sort |
enhancing the anticancer activity of antrodia cinnamomea in hepatocellular carcinoma cells via cocultivation with ginger: the impact on cancer cell survival pathways |
publisher |
Frontiers Media S.A. |
series |
Frontiers in Pharmacology |
issn |
1663-9812 |
publishDate |
2018-07-01 |
description |
Antrodia cinnamomea (AC) is a medicinal fungal species that has been widely used traditionally in Taiwan for the treatment of diverse health-related conditions including cancer. It possesses potent anti-inflammatory and antioxidant properties in addition to its ability to promote cancer cell death in several human tumors. Our aim was to improve the anticancer activity of AC in hepatocellular carcinoma (HCC) through its cocultivation with ginger aiming at tuning the active ingredients. HCC cell lines, Huh-7 and HepG2 were used to study the in vitro anticancer activity of the ethanolic extracts of AC (EAC) alone or after the cocultivation in presence of ginger (EACG). The results indicated that the cocultivation of AC with ginger significantly induced the production of important triterpenoids and EACG was significantly more potent than EAC in targeting HCC cell lines. EACG effectively inhibited cancer cells growth via the induction of cell cycle arrest at G2/M phase and induction of apoptosis in Huh-7 and HepG2 cells as indicated by MTT assay, cell cycle analysis, Annexin V assay, and the activation of caspase-3. In addition, EACG modulated cyclin proteins expression and mitogen-activated protein kinase (MAPK) signaling pathways in favor of the inhibition of cancer cell survival. Taken together, the current study highlights an evidence that EACG is superior to EAC in targeting cancer cell survival and inducing apoptotic cell death in HCC. These findings support that EACG formula can serve as a potential candidate for HCC adjuvant therapy. |
topic |
Antrodia cinnamomea ginger hepatocellular carcinoma apoptosis cell cycle MAPK |
url |
https://www.frontiersin.org/article/10.3389/fphar.2018.00780/full |
work_keys_str_mv |
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