Inhibition of Wnt/ββ-catenin signaling by monensin in cervical cancer
10.4196/kjpp.2024.28.1.21
- Author:
Bingbing FU
1
;
Lixia FANG
;
Ranran WANG
;
Xueling ZHANG
Author Information
1. Department of Obstetrics and Gynaecology, Xiangyang Central Hospital, Affiliated Hospital of Hubei University of Arts and Science, Xiangyang, Hubei 441000, China
- Publication Type:Original Article
- From:The Korean Journal of Physiology and Pharmacology
2024;28(1):21-30
- CountryRepublic of Korea
- Language:EN
-
Abstract:
The challenging clinical outcomes associated with advanced cervical cancer underscore the need for a novel therapeutic approach. Monensin, a polyether antibiotic, has recently emerged as a promising candidate with anti-cancer properties. In line with these ongoing efforts, our study presents compelling evidence of monensin's potent efficacy in cervical cancer. Monensin exerts a pronounced inhibitory impact on proliferation and anchorage-independent growth. Additionally, monensin significantly inhibited cervical cancer growth in vivo without causing any discernible toxicity in mice. Mechanism studies show that monensin's anti-cervical cancer activity can be attributed to its capacity to inhibit the Wnt/β-catenin pathway, rather than inducing oxidative stress. Monensin effectively reduces both the levels and activity of β-catenin, and we identify Akt, rather than CK1, as the key player involved in monensin-mediated Wnt/β-catenin inhibition. Rescue studies using Wnt activator and β-catenin-overexpressing cells confirmed that β-catenin inhibition is the mechanism of monensin’s action. As expected, cervical cancer cells exhibiting heightened Wnt/β-catenin activity display increased sensitivity to monensin treatment. In conclusion, our findings provide pre-clinical evidence that supports further exploration of monensin's potential for repurposing in cervical cancer therapy, particularly for patients exhibiting aberrant Wnt/β-catenin activation.
