Theabrownins Produced via Chemical Oxidation of Tea Polyphenols Inhibit Human Lung Cancer Cells in vivo and in vitro by Suppressing the PI3K/AKT/mTOR Pathway Activation and Promoting Autophagy
During the fermentation of dark tea, theabrownins (TBs), carbohydrates, and other substances get irreversibly complex. Recent research on the biological activity of TBs is not based on free TBs. In the present study, some brown polyphenol oxidized polymers, the generalized TBs (TBs-C), were prepared...
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Frontiers Media S.A.
2022-04-01
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Online Access: | https://www.frontiersin.org/articles/10.3389/fnut.2022.858261/full |
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author | Yongyong Wang Yao Yuan Yao Yuan Chunpeng Wang Chunpeng Wang Bingjie Wang Bingjie Wang Wenbin Zou Ni Zhang Xiaoqiang Chen Xiaoqiang Chen |
author_facet | Yongyong Wang Yao Yuan Yao Yuan Chunpeng Wang Chunpeng Wang Bingjie Wang Bingjie Wang Wenbin Zou Ni Zhang Xiaoqiang Chen Xiaoqiang Chen |
author_sort | Yongyong Wang |
collection | DOAJ |
description | During the fermentation of dark tea, theabrownins (TBs), carbohydrates, and other substances get irreversibly complex. Recent research on the biological activity of TBs is not based on free TBs. In the present study, some brown polyphenol oxidized polymers, the generalized TBs (TBs-C), were prepared via alkali oxidation from tea polyphenols (TP). We also investigated the inhibitory mechanism of TBs-C on non-small-cell-lung cancer (NSCLC). TBs-C demonstrated a stronger inhibition than TP on the NSCLC cell lines A549, H2030, HCC827, H1975, and PC9. Next, A549 and H2030 cell lines were selected as subjects to explore this mechanism. TBs-C was found to inhibit proliferation, promote apoptosis, and induce G1 cell-cycle arrest in the cells. In addition, TBs-C increased autophagic flux, which in turn promoted the death of lung cancer cells. Moreover, TBs-C suppressed the PI3K/AKT/mTOR pathway activation, promoted autophagy, and increased the expression of p21 downstream of AKT, which resulted in G1 cell-cycle arrest. In xenotransplanted NSCLC nude mice derived from A549 cells, TBs-C could significantly suppress tumor growth by inhibiting the PI3K/AKT/mTOR pathway without causing hepatotoxicity, brain toxicity, or nephrotoxicity. We believe that our present findings would facilitate advancement in the research and industrialization of TBs. |
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publishDate | 2022-04-01 |
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spelling | doaj.art-4096f8d8d37249d29455ec2bcbded0292022-12-22T02:45:43ZengFrontiers Media S.A.Frontiers in Nutrition2296-861X2022-04-01910.3389/fnut.2022.858261858261Theabrownins Produced via Chemical Oxidation of Tea Polyphenols Inhibit Human Lung Cancer Cells in vivo and in vitro by Suppressing the PI3K/AKT/mTOR Pathway Activation and Promoting AutophagyYongyong Wang0Yao Yuan1Yao Yuan2Chunpeng Wang3Chunpeng Wang4Bingjie Wang5Bingjie Wang6Wenbin Zou7Ni Zhang8Xiaoqiang Chen9Xiaoqiang Chen10Department of Thoracic Surgery, Tongji Hospital, Tongji Medical College, Huazhong University of Science and Technology, Wuhan, ChinaNational “111” Center for Cellular Regulation and Molecular Pharmaceutics, Key Laboratory of Fermentation Engineering, Ministry of Education, Hubei University of Technology, Wuhan, ChinaBeijing Engineering and Technology Research Center of Food Additives, Beijing Technology and Business University (BTBU), Beijing, ChinaNational “111” Center for Cellular Regulation and Molecular Pharmaceutics, Key Laboratory of Fermentation Engineering, Ministry of Education, Hubei University of Technology, Wuhan, ChinaBeijing Engineering and Technology Research Center of Food Additives, Beijing Technology and Business University (BTBU), Beijing, ChinaNational “111” Center for Cellular Regulation and Molecular Pharmaceutics, Key Laboratory of Fermentation Engineering, Ministry of Education, Hubei University of Technology, Wuhan, ChinaBeijing Engineering and Technology Research Center of Food Additives, Beijing Technology and Business University (BTBU), Beijing, ChinaDepartment of Thoracic Surgery, Tongji Hospital, Tongji Medical College, Huazhong University of Science and Technology, Wuhan, ChinaDepartment of Thoracic Surgery, Tongji Hospital, Tongji Medical College, Huazhong University of Science and Technology, Wuhan, ChinaNational “111” Center for Cellular Regulation and Molecular Pharmaceutics, Key Laboratory of Fermentation Engineering, Ministry of Education, Hubei University of Technology, Wuhan, ChinaBeijing Engineering and Technology Research Center of Food Additives, Beijing Technology and Business University (BTBU), Beijing, ChinaDuring the fermentation of dark tea, theabrownins (TBs), carbohydrates, and other substances get irreversibly complex. Recent research on the biological activity of TBs is not based on free TBs. In the present study, some brown polyphenol oxidized polymers, the generalized TBs (TBs-C), were prepared via alkali oxidation from tea polyphenols (TP). We also investigated the inhibitory mechanism of TBs-C on non-small-cell-lung cancer (NSCLC). TBs-C demonstrated a stronger inhibition than TP on the NSCLC cell lines A549, H2030, HCC827, H1975, and PC9. Next, A549 and H2030 cell lines were selected as subjects to explore this mechanism. TBs-C was found to inhibit proliferation, promote apoptosis, and induce G1 cell-cycle arrest in the cells. In addition, TBs-C increased autophagic flux, which in turn promoted the death of lung cancer cells. Moreover, TBs-C suppressed the PI3K/AKT/mTOR pathway activation, promoted autophagy, and increased the expression of p21 downstream of AKT, which resulted in G1 cell-cycle arrest. In xenotransplanted NSCLC nude mice derived from A549 cells, TBs-C could significantly suppress tumor growth by inhibiting the PI3K/AKT/mTOR pathway without causing hepatotoxicity, brain toxicity, or nephrotoxicity. We believe that our present findings would facilitate advancement in the research and industrialization of TBs.https://www.frontiersin.org/articles/10.3389/fnut.2022.858261/fulltheabrowninschemical oxidationtea polyphenolshuman lung cancerin vivo and in vitro |
spellingShingle | Yongyong Wang Yao Yuan Yao Yuan Chunpeng Wang Chunpeng Wang Bingjie Wang Bingjie Wang Wenbin Zou Ni Zhang Xiaoqiang Chen Xiaoqiang Chen Theabrownins Produced via Chemical Oxidation of Tea Polyphenols Inhibit Human Lung Cancer Cells in vivo and in vitro by Suppressing the PI3K/AKT/mTOR Pathway Activation and Promoting Autophagy Frontiers in Nutrition theabrownins chemical oxidation tea polyphenols human lung cancer in vivo and in vitro |
title | Theabrownins Produced via Chemical Oxidation of Tea Polyphenols Inhibit Human Lung Cancer Cells in vivo and in vitro by Suppressing the PI3K/AKT/mTOR Pathway Activation and Promoting Autophagy |
title_full | Theabrownins Produced via Chemical Oxidation of Tea Polyphenols Inhibit Human Lung Cancer Cells in vivo and in vitro by Suppressing the PI3K/AKT/mTOR Pathway Activation and Promoting Autophagy |
title_fullStr | Theabrownins Produced via Chemical Oxidation of Tea Polyphenols Inhibit Human Lung Cancer Cells in vivo and in vitro by Suppressing the PI3K/AKT/mTOR Pathway Activation and Promoting Autophagy |
title_full_unstemmed | Theabrownins Produced via Chemical Oxidation of Tea Polyphenols Inhibit Human Lung Cancer Cells in vivo and in vitro by Suppressing the PI3K/AKT/mTOR Pathway Activation and Promoting Autophagy |
title_short | Theabrownins Produced via Chemical Oxidation of Tea Polyphenols Inhibit Human Lung Cancer Cells in vivo and in vitro by Suppressing the PI3K/AKT/mTOR Pathway Activation and Promoting Autophagy |
title_sort | theabrownins produced via chemical oxidation of tea polyphenols inhibit human lung cancer cells in vivo and in vitro by suppressing the pi3k akt mtor pathway activation and promoting autophagy |
topic | theabrownins chemical oxidation tea polyphenols human lung cancer in vivo and in vitro |
url | https://www.frontiersin.org/articles/10.3389/fnut.2022.858261/full |
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