New small-molecule compound Hu-17 inhibits estrogen biosynthesis by aromatase in human ovarian granulosa cancer cells.
Activating Transcription Factor 2
/ metabolism
Antineoplastic Agents, Hormonal
/ pharmacology
Apoptosis
/ drug effects
Aromatase
/ genetics
Aromatase Inhibitors
/ pharmacology
Cell Line, Tumor
Cell Proliferation
/ drug effects
Estrogens
/ biosynthesis
Extracellular Signal-Regulated MAP Kinases
/ metabolism
Female
Gene Expression Regulation, Neoplastic
Granulosa Cell Tumor
/ drug therapy
Humans
Ovarian Neoplasms
/ drug therapy
Phosphorylation
Proteasome Endopeptidase Complex
/ metabolism
Proteolysis
Signal Transduction
CYP19A1
apoptosis
estrogen
ovarian granulosa cancer
Journal
Cancer medicine
ISSN: 2045-7634
Titre abrégé: Cancer Med
Pays: United States
ID NLM: 101595310
Informations de publication
Date de publication:
12 2020
12 2020
Historique:
received:
11
10
2019
revised:
17
07
2020
accepted:
08
09
2020
pubmed:
2
10
2020
medline:
22
7
2021
entrez:
1
10
2020
Statut:
ppublish
Résumé
Estrogen-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-dependent 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 Similarity 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 invasive ovarian granulosa cell carcinoma. Hu-17 reduced the expression of CYP19A1 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 aromatase activity. Therefore, Hu-17 could serve as a potential treatment for estrogen-dependent cancers albeit further investigation is warranted.
Identifiants
pubmed: 33002342
doi: 10.1002/cam4.3492
pmc: PMC7724309
doi:
Substances chimiques
ATF2 protein, human
0
Activating Transcription Factor 2
0
Antineoplastic Agents, Hormonal
0
Aromatase Inhibitors
0
Estrogens
0
Aromatase
EC 1.14.14.1
CYP19A1 protein, human
EC 1.14.14.1
Extracellular Signal-Regulated MAP Kinases
EC 2.7.11.24
Proteasome Endopeptidase Complex
EC 3.4.25.1
Types de publication
Journal Article
Research Support, Non-U.S. Gov't
Langues
eng
Sous-ensembles de citation
IM
Pagination
9081-9095Informations de copyright
© 2020 The Authors. Cancer Medicine published by John Wiley & Sons Ltd.
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