New small ‐molecule compound Hu‐17 inhibits estrogen biosynthesis by aromatase in human ovarian granulosa cancer cells

The present study suggests that Hu ‐17 inhibits estrogen biosynthesis by decreasing aromatase expression and destabilizing aromatase protein to inhibit cell proliferation and induce cell apoptosis in KGN cells, and it warrants further investigation as potential treatment for estrogen‐dependent cancers. AbstractEstrogen ‐dependent cancers (breast, endometrial, and ovarian) are among the leading causes of morbidity and mortality in women worldwide. Aromatase is the main enzyme that catalyzes the biosynthesis of estrogen, which drives proliferation, and antiestrogens can inhibit the growth of these estrogen‐depen dent cancers. Hu‐17, an aromatase inhibitor, is a novel small‐molecule compound that suppresses viability of and promotes apoptosis in ovarian cancer cells. Therefore, this study aimed to predict targets of Hu‐17 and assess its intracellular signaling in ovarian cancer cells. Using the Similar ity Ensemble Approach software to predict the potential mechanism of Hu‐17 and combining phospho‐proteome arrays with western blot analysis, we observed that Hu‐17 could inhibit the ERK pathway, resulting in reduced estrogen synthesis in KGN cells, a cell line derived from a patient with invas ive ovarian granulosa cell carcinoma. Hu‐17 reduced the expression ofCYP19A1 mRNA, responsible for producing aromatase, by suppressing the phosphorylation of cAMP response element binding ‐1. Hu‐17 also accelerated aromatase protein degradation but had no effect on ...
Source: Cancer Medicine - Category: Cancer & Oncology Authors: Tags: ORIGINAL RESEARCH Source Type: research