title: Isoliquiritigenin induces apoptosis and autophagy and inhibits endometrial cancer growth in mice.
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 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.
authors.affiliation: School of Nutrition and Health Sciences, College of Nutrition, Taipei Medical University, Taipei, Taiwan.
authors.forename: Chi-Hao
authors.initials: CH
authors.lastname: Wu
authors.affiliation: School of Nutrition and Health Sciences, College of Nutrition, Taipei Medical University, Taipei, Taiwan.
authors.forename: Hsin-Yuan
authors.initials: HY
authors.lastname: Chen
authors.affiliation: Graduate Institute of Clinical Medicine, College of Medicine, Taipei Medical University, Taipei, Taiwan.|Department of Obstetrics and Gynecology, School of Medicine, College of Medicine, Taipei Medical University, Taipei, Taiwan.|Department of Obstetrics and Gynecology, Taipei Medical University Hospital, Taipei, Taiwan.
authors.forename: Chia-Woei
authors.initials: CW
authors.lastname: Wang
authors.affiliation: Department of Dental Hygiene, College of Health Care, China Medical University, Taichung, Taiwan.
authors.forename: Tzong-Ming
authors.initials: TM
authors.lastname: Shieh
authors.affiliation: PhD Program for Cancer Biology and Drug Discovery, College of Medical Science and Technology, Taipei Medical University and Academia Sinica, Taipei, Taiwan.
authors.forename: Tsui-Chin
authors.initials: TC
authors.lastname: Huang
authors.affiliation: School of Nutrition and Health Sciences, College of Nutrition, Taipei Medical University, Taipei, Taiwan.
authors.forename: Li-Chun
authors.initials: LC
authors.lastname: Lin
authors.affiliation: School of Nutrition and Health Sciences, College of Nutrition, Taipei Medical University, Taipei, Taiwan.
authors.forename: Kai-Lee
authors.initials: KL
authors.lastname: Wang
authors.affiliation: School of Nutrition and Health Sciences, College of Nutrition, Taipei Medical University, Taipei, Taiwan.
authors.forename: Shih-Min
authors.initials: SM
authors.lastname: Hsia
mesh_terms: D000818:Animals; D000972:Antineoplastic Agents, Phytogenic / Q000494:pharmacology*; D017209:Apoptosis / Q000187:drug effects*; D001343:Autophagy / Q000187:drug effects*; D059447:Cell Cycle Checkpoints / Q000187:drug effects; D045744:Cell Line, Tumor; D049109:Cell Proliferation / Q000187:drug effects; D047188:Chalcones / Q000494:pharmacology*; D004249:DNA Damage / Q000187:drug effects; D004195:Disease Models, Animal; D016889:Endometrial Neoplasms; D005260:Female; D006801:Humans; D051379:Mice; D008954:Models, Biological; D023041:Xenograft Model Antitumor Assays
chemical_list: D000972:Antineoplastic Agents, Phytogenic; D047188:Chalcones; C040920:isoliquiritigenin
keywords: apoptosis; autophagy; endometrial cancer; isoliquiritigenin