Isoliquiritigenin induces apoptosis and autophagy and inhibits endometrial cancer growth in mice

Chi-Hao Wu, Hsin Yuan Chen, Chia-Woei Wang, Tzong Ming Shieh, Tsui-Chin Huang, Li Chun Lin, Kai Lee Wang, Shih-Min Hsia

Research output: Contribution to journalArticle

35 Citations (Scopus)

Abstract

Endometrial cancer is the most common cancer in women, typically with onset after menopause. Isoliquiritigenin (ISL), a licorice flavonoid, was previously shown to have anti-oxidant, anti-inflammatory, and tumor suppression effects. In this study, we investigated the anti-tumor effect of ISL on human endometrial cancer both in vitro and in vivo. We used telomerase-immortalized human endometrial stromal cells (T-HESCs) and human endometrial cancer cell lines (Ishikawa, HEC-1A, and RL95-2 cells) as targets. The effects of ISL on cell proliferation, cell cycle regulation, and apoptosis or autophagy-related protein expression were examined. In addition, we conducted in vivo experiments to confirm the inhibitory effects of ISL on cancer cells. ISL significantly inhibited the viability of cancer cells in a dose- and timedependent manner but with little toxicity on normal cells. In addition, flow cytometry analysis indicated that ISL induced sub-G1 or G2/M phase arrest. ISL treatment activated the extracellular signal regulated kinase signaling pathway to enhance the protein expression of caspase-7/LC3BII associated with apoptosis/autophagy. Furthermore, ISL suppressed xenograft tumor growth in vivo. Taken together, these findings suggest that ISL may induce apoptosis, autophagy, and cell growth inhibition, indicating its potential as a therapeutic agent for human endometrial cancer.

Original languageEnglish
Pages (from-to)73432-73447
Number of pages16
JournalOncotarget
Volume7
Issue number45
DOIs
Publication statusPublished - 2016

Keywords

  • Apoptosis
  • Autophagy
  • Endometrial cancer
  • Isoliquiritigenin

ASJC Scopus subject areas

  • Oncology

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