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

Kai-Lee Wang¹  Yong-Han Hong²  Tsui-Chin Huang³  Tzong-Ming Shieh⁴  Hsin-Yuan Chen⁵  Yi-Fen Chiang⁵  Chun-Kuang Shih⁵  Sing-Chung Li⁵  Shih-Min Hsia⁵  Po-Han Lin⁵  Tong-Hong Wang⁶ 

[1] Department of Nursing, Ching Kuo Institute of Management and Health, Keelung City 20301, Taiwan;Department of Nutrition, I-Shou University, Kaohsiung City 82445, Taiwan;Graduate Institute of Cancer Biology and Drug Discovery, College of Medical Science and Technology, Taipei Medical University, Taipei 11031, Taiwan;School of Dentistry, College of Dentistry, China Medical University, Taichung 40402, Taiwan;School of Nutrition and Health Sciences, College of Nutrition, Taipei Medical University, Taipei 11031, Taiwan;Tissue Bank, Chang Gung Memorial Hospital, Tao-Yuan 33305, Taiwan;

关键词: isoliquiritigenin (isl);    triple-negative breast cancer;    apoptosis;    autophagy;   

DOI  :  10.3390/antiox9030228

来源: DOAJ

【 摘 要 】

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.

【 授权许可】

Unknown