Enterolactone has stronger effects than enterodiol on ovarian cancer
Authors: Xiaoyu Wang
Yongfang Liu
Hong-Xia Bao
Yu-Jie Zhou
Miao Yu
Sijing Hu
Qing-Hai Li
Shan Gao
Tingting Gao
Zheng Zeng
Hongyue Wang
Zhihang Shen
Huidi Liu
Ting Li
Siwen Wang
Jianrui Liu
Emilio Mastriani
Yingying Qi
Randal N Johnston
Shu-Lin Liu
Journal: Journal of Ovarian Research (2017)
Discipline: BIOLOGY & BIOCHEMISTRY
Keywords: Anti-cancer; Enterodiol; Enterolactone; Ovarian cancer.
Affiliations: Systemomics Center, College of Pharmacy, and Genomics Research Center (State-Province Key Laboratories of Biomedicine-Pharmaceutics of China), Harbin Medical University, Harbin, 150081, China., HMU-UCFM Centre for Infection and Genomics, Harbin, China., Department of Biochemistry and Molecular Biology, University of Calgary, T2N1N4, Calgary, Canada., Current address: Department of Biomedical Sciences, University of Calgary, T2N1N4, Calgary, Canada., Systemomics Center, College of Pharmacy, and Genomics Research Center (State-Province Key Laboratories of Biomedicine-Pharmaceutics of China), Harbin Medical University, Harbin, 150081, China. ., HMU-UCFM Centre for Infection and Genomics, Harbin, China. ., Department of Microbiology, Immunology and Infectious Diseases, University of Calgary, T2N1N4, Calgary, Canada. .

Abstract:  Background: Ovarian cancer is one of the three leading gynecological malignancies, characterized by insidious growth, highly frequent metastasis, and quick development of drug resistance. As a result, this disease has low 5-year survival rates. Estrogen receptor inhibitors were commonly used for the treatment, but only 7% to 18% of patients respond to anti-estrogen therapies. Therefore, more effective therapies to inhibit estrogen-related tumors are urgently needed. Recently, phytoestrogens, such as lignans with estrogen-like biological activities, have attracted attention for their potential effects in the prevention or treatment of estrogen-related diseases. Enterodiol (END) and enterolactone (ENL) are mammalian lignans, which can reduce the risk of various cancers. However, the effects of END and ENL on ovarian cancer are not adequately documented. Methods: We used in vitro assays on the ES-2 cell line to evaluate the inhibiting effects of END and ENL on ovarian cancer cell proliferation, invasion and migration ability and in vivo xenograft experiments on nude mice to validate the anticancer effects of END and ENL. Results: The in vitro assays demonstrated that high-dose END and ENL could obviously inhibit ovarian malignant properties, including cancerous proliferation, invasion, and metastasis. Compared to END, ENL behaved in a better time-dose dependent manner on the cancer cells. The in vivo experiments showed that END (1 mg/kg), ENL (1 mg/kg) and ENL (0.1 mg/kg) suppressed tumor markedly, and there were statistically significant differences between the experimental and control groups in tumor weight and volume. Compared to END, which have serious side effects to the animals at high concentration such as 1 mg/kg, ENL had higher anticancer activities and less side effects in the animals than END at the same concentrations, so it would be a better candidate for drug development. Conclusion: END and ENL both have potent inhibitory effects on ovarian cancer but ENL possesses a more effective anti-cancer capability and less side effects than END. Findings in this work provide novel insights into ovarian cancer therapeutics with phytoestrogens and encourage their clinical applications. 

Retracted: No

PubPeer comments:
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