β-catenin signaling inhibitors ICG-001 and C-82 improve fibrosis in preclinical models of endometriosis.

Abstract

Endometriosis exhibits unique characteristics, such as fibrosis, resistance to apoptosis, and promotion of cell proliferation; however, its pathophysiology is not fully understood. Recurrence rates after treatment are high, and the progression risk continues until menopause; hence, more effective therapy for endometriosis is needed. CREB-binding protein (CBP)/β-catenin signaling inhibitors have demonstrated antifibrogenetic effects in liver, lung, and skin diseases. The present study evaluated the effects of two CBP/β-catenin signaling inhibitors, ICG-001 and C-82, on the progression of endometriosis using endometriotic cyst stromal cells from the ovary and normal endometrial stromal cells from the uterus. ICG-001 was also evaluated in a mouse model. ICG-001 and C-82 inhibited cell proliferation, fibrogenesis, and cell migration, and promoted apoptosis in vitro. ICG-001 inhibited the growth of endometriotic lesions in the mouse model. CBP/β-catenin signaling plays an important role in the pathophysiology of endometriosis. Inhibiting the CBP/β-catenin signal can be a therapeutic target for endometriosis.

• Authors: Tomoko Hirakawa, Kaei Nasu, Saori Miyabe, Hiroyuki Kouji, Akira Katoh, Naoto Uemura, Hisashi Narahara
• Journal: Scientific reports (Sci Rep) Vol. 9 Issue 1 Pg. 20056 (12 27 2019) ISSN: 2045-2322 [Electronic] England
• PMID: 31882904 (Publication Type: Journal Article, Research Support, Non-U.S. Gov't)

Chemical References

• Bridged Bicyclo Compounds, Heterocyclic
• C82 compound
• CTNNB1 protein, human
• Heterocyclic Compounds, 2-Ring
• ICG 001
• Piperazines
• Pyrimidinones
• beta Catenin

Topics

• Animals
• Bridged Bicyclo Compounds, Heterocyclic (therapeutic use)
• Disease Models, Animal
• Endometriosis (drug therapy)
• Female
• Heterocyclic Compounds, 2-Ring (therapeutic use)
• Humans
• Mice
• Piperazines (therapeutic use)
• Pyrimidinones (therapeutic use)
• Signal Transduction (drug effects)
• beta Catenin (antagonists & inhibitors, metabolism)