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

Po-Han Lin; 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; Shih-Min Hsia

doi:10.3390/antiox9030228

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 (Basel). 2020 Mar 10;9(3):228. doi: 10.3390/antiox9030228.

Authors

Po-Han Lin¹, Yi-Fen Chiang¹, Tzong-Ming Shieh^{2

3}, Hsin-Yuan Chen¹, Chun-Kuang Shih¹, Tong-Hong Wang^{4

5}, Kai-Lee Wang⁶, Tsui-Chin Huang⁷, Yong-Han Hong⁸, Sing-Chung Li¹, Shih-Min Hsia^{1

9

10

11}

Affiliations

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.

Abstract

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.

Keywords: apoptosis; autophagy; isoliquiritigenin (ISL); triple-negative breast cancer.