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Article

Dietary Compound Isoliquiritigenin, an Antioxidant from Licorice, Suppresses Triple-Negative Breast Tumor Growth via Apoptotic Death Program Activation in Cell and Xenograft Animal Models

1
School of Nutrition and Health Sciences, College of Nutrition, Taipei Medical University, Taipei 11031, Taiwan
2
School of Dentistry, College of Dentistry, China Medical University, Taichung 40402, Taiwan
3
Department of Dental Hygiene, College of Health Care, China Medical University, Taichung 40402, Taiwan
4
Tissue Bank, Chang Gung Memorial Hospital, Tao-Yuan 33305, Taiwan
5
Graduate Institute of Health Industry Technology, Chang Gung University of Science and Technology, Tao-Yuan 33305, Taiwan
6
Department of Nursing, Ching Kuo Institute of Management and Health, Keelung City 20301, Taiwan
7
Graduate Institute of Cancer Biology and Drug Discovery, College of Medical Science and Technology, Taipei Medical University, Taipei 11031, Taiwan
8
Department of Nutrition, I-Shou University, Kaohsiung City 82445, Taiwan
9
Graduate Institute of Metabolism and Obesity Sciences, College of Nutrition, Taipei Medical University, Taipei 11031, Taiwan
10
School of Food Safety, College of Nutrition, Taipei Medical University, Taipei 11031, Taiwan
11
Nutrition Research Center, Taipei Medical University Hospital, Taipei 11031, Taiwan
*
Author to whom correspondence should be addressed.
These authors equal contribution as the first author in this study.
Antioxidants 2020, 9(3), 228; https://doi.org/10.3390/antiox9030228
Received: 22 January 2020 / Revised: 16 February 2020 / Accepted: 7 March 2020 / Published: 10 March 2020
(This article belongs to the Special Issue Natural Phenolic Compounds for Health, Food and Cosmetic Applications)
Patients with triple-negative breast cancer have few therapeutic strategy options. In this study, we investigated the effect of isoliquiritigenin (ISL) on the proliferation of triple-negative breast cancer cells. We found that treatment with ISL inhibited triple-negative breast cancer cell line (MDA-MB-231) cell growth and increased cytotoxicity. ISL reduced cell cycle progression through the reduction of cyclin D1 protein expression and increased the sub-G1 phase population. The ISL-induced apoptotic cell population was observed by flow cytometry analysis. The expression of Bcl-2 protein was reduced by ISL treatment, whereas the Bax protein level increased; subsequently, the downstream signaling molecules caspase-3 and poly ADP-ribose polymerase (PARP) were activated. Moreover, ISL reduced the expression of total and phosphorylated mammalian target of rapamycin (mTOR), ULK1, and cathepsin B, whereas the expression of autophagic-associated proteins p62, Beclin1, and LC3 was increased. The decreased cathepsin B cause the p62 accumulation to induce caspase-8 mediated apoptosis. In vivo studies further showed that preventive treatment with ISL could inhibit breast cancer growth and induce apoptotic and autophagic-mediated apoptosis cell death. Taken together, ISL exerts an effect on the inhibition of triple-negative MDA-MB-231 breast cancer cell growth through autophagy-mediated apoptosis. Therefore, future studies of ISL as a supplement or alternative therapeutic agent for clinical trials against breast cancer are warranted. View Full-Text
Keywords: isoliquiritigenin (ISL); triple-negative breast cancer; apoptosis; autophagy isoliquiritigenin (ISL); triple-negative breast cancer; apoptosis; autophagy
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MDPI and ACS Style

Lin, P.-H.; Chiang, Y.-F.; Shieh, T.-M.; Chen, H.-Y.; Shih, C.-K.; Wang, T.-H.; Wang, K.-L.; Huang, T.-C.; Hong, Y.-H.; Li, S.-C.; Hsia, S.-M. Dietary Compound Isoliquiritigenin, an Antioxidant from Licorice, Suppresses Triple-Negative Breast Tumor Growth via Apoptotic Death Program Activation in Cell and Xenograft Animal Models. Antioxidants 2020, 9, 228. https://doi.org/10.3390/antiox9030228

AMA Style

Lin P-H, Chiang Y-F, Shieh T-M, Chen H-Y, Shih C-K, Wang T-H, Wang K-L, Huang T-C, Hong Y-H, Li S-C, Hsia S-M. Dietary Compound Isoliquiritigenin, an Antioxidant from Licorice, Suppresses Triple-Negative Breast Tumor Growth via Apoptotic Death Program Activation in Cell and Xenograft Animal Models. Antioxidants. 2020; 9(3):228. https://doi.org/10.3390/antiox9030228

Chicago/Turabian Style

Lin, Po-Han, Yi-Fen Chiang, Tzong-Ming Shieh, Hsin-Yuan Chen, Chun-Kuang Shih, Tong-Hong Wang, Kai-Lee Wang, Tsui-Chin Huang, Yong-Han Hong, Sing-Chung Li, and Shih-Min Hsia. 2020. "Dietary Compound Isoliquiritigenin, an Antioxidant from Licorice, Suppresses Triple-Negative Breast Tumor Growth via Apoptotic Death Program Activation in Cell and Xenograft Animal Models" Antioxidants 9, no. 3: 228. https://doi.org/10.3390/antiox9030228

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