Enterolactone has stronger effects than enterodiol on ovarian cancer

Abstract

BackgroundOvarian 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.MethodsWe 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.ResultsThe 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.ConclusionEND 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: Role of CXCL12–CXCR4 axis in ovarian cancer metastasis and CXCL12–CXCR4 blockade with AMD3100 suppresses tumor cell migration and invasion in vitro

“…Ovarian cancer (OC) is a malignancy with features of insidious growth, highly frequent metastasis, and quick development of drug resistance, which accounts for the No. 1 mortality among all gynecological cancers, the fifth leading cause of cancer among females (H. Liu et al, ). Almost 200,000 women suffered the cancer of ovary worldwide, and it is so lethal that over 100,000 deaths related to it each year (Bhatt & Glehen, ).…”

Phytoestrogen Concentrations in Human Urine as Biomarkers for Dietary Phytoestrogen Intake in Mexican Women

“…The biological activity of enterolactone and enterodiol is different; enterolactone is a more potent aromatase inhibitor and has approximately 10 times the estrogenic activity than enterodiol [ 53 ]. According to Liu et al [ 54 ], enterodiol and enterolactone both have potent inhibitory effects on ovarian cancer, but enterolactone possesses a more effective anti-cancer capability and fewer side effects than enterodiol. Enterolactone also has inhibitory effects on growth and metastasis in human breast cancer [ 55 ].…”

Association of serum lipids and severity of epithelial ovarian cancer: an observational cohort study of 349 Chinese patients

“…Ovarian cancer is one of the most lethal gynecological malignancies worldwide, with an estimated 21,290 new diagnoses of ovarian cancer and 14,180 deaths anticipated for 2015 in the United States [ 1 ] . Epithelial ovarian cancer (EOC) accounts for 90% of ovarian cancer cases, with serous cancer accounting for the most common histology type [ 2 ] . Most women present with advanced-stage disease at the time of diagnosis, resulting in elevated mortality rates [ 3 ] .…”