Research Papers:

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 and Shih-Min Hsia _

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Oncotarget. 2016; 7:73432-73447. https://doi.org/10.18632/oncotarget.12369

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Chi-Hao Wu1,*, Hsin-Yuan Chen1,*, Chia-Woei Wang2,3,4,*, Tzong-Ming Shieh5, Tsui-Chin Huang6, Li-Chun Lin1, Kai-Lee Wang1, Shih-Min Hsia1

1School of Nutrition and Health Sciences, College of Nutrition, Taipei Medical University, Taipei, Taiwan

2Graduate Institute of Clinical Medicine, College of Medicine, Taipei Medical University, Taipei, Taiwan

3Department of Obstetrics and Gynecology, School of Medicine, College of Medicine, Taipei Medical University, Taipei, Taiwan

4Department of Obstetrics and Gynecology, Taipei Medical University Hospital, Taipei, Taiwan

5Department of Dental Hygiene, College of Health Care, China Medical University, Taichung, Taiwan

6PhD Program for Cancer Biology and Drug Discovery, College of Medical Science and Technology, Taipei Medical University and Academia Sinica, Taipei, Taiwan

*These authors contributed equally to this work

Correspondence to:

Shih-Min Hsia, email: [email protected]

Keywords: endometrial cancer, isoliquiritigenin, apoptosis, autophagy

Received: June 20, 2016     Accepted: September 25, 2016     Published: September 30, 2016


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 time-dependent 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.

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