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

• Published in: Oncotarget Vol. 7; no. 45; pp. 73432 - 73447
• Main Authors: Wu, Chi-Hao, Chen, Hsin-Yuan, Wang, Chia-Woei, Shieh, Tzong-Ming, Huang, Tsui-Chin, Lin, Li-Chun, Wang, Kai-Lee, Hsia, Shih-Min
• Format: Journal Article
• Language: English
• Published: United States Impact Journals LLC 08.11.2016
• Subjects: Animals; Antineoplastic Agents, Phytogenic - pharmacology; Apoptosis - drug effects; Autophagy - drug effects; Cell Cycle Checkpoints - drug effects; Cell Line, Tumor; Cell Proliferation - drug effects; Chalcones - pharmacology; Disease Models, Animal; DNA Damage - drug effects; Endometrial Neoplasms; Female; Humans; Mice; Models, Biological; Research Paper; Xenograft Model Antitumor Assays; endometrial cancer; apoptosis; autophagy; isoliquiritigenin
• ISSN: 1949-2553; 1949-2553
• DOI: 10.18632/oncotarget.12369

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.