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

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1 Citation (Scopus)

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.

Original languageEnglish
Article number228
JournalAntioxidants
Volume9
Issue number3
DOIs
Publication statusPublished - Mar 10 2020

Keywords

  • Apoptosis
  • Autophagy
  • Isoliquiritigenin (ISL)
  • Triple-negative breast cancer

ASJC Scopus subject areas

  • Biochemistry
  • Physiology
  • Molecular Biology
  • Clinical Biochemistry
  • Cell Biology

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