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- Title
Inhibition of Wnt/β-catenin signaling by monensin in cervical cancer.
- Authors
Bingbing Fu; Lixia Fang; Ranran Wang; Xueling Zhang
- 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/ß-catenin pathway, rather than inducing oxidative stress. Monensin effectively reduces both the levels and activity of ß-catenin, and we identify Akt, rather than CK1, as the key player involved in monensin-mediated Wnt/ß-catenin inhibition. Rescue studies using Wnt activator and ß-catenin-overexpressing cells confirmed that ß-catenin inhibition is the mechanism of monensin's action. As expected, cervical cancer cells exhibiting heightened Wnt/ß-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/ß-catenin activation.
- Subjects
CERVICAL cancer; MONENSIN; TUMOR growth; OXIDATIVE stress; WNT proteins; CANCER treatment; WNT signal transduction; CATENINS
- Publication
Korean Journal of Physiology & Pharmacology, 2024, Vol 28, Issue 1, p21
- ISSN
1226-4512
- Publication type
Article
- DOI
10.4196/kjpp.2024.28.1.21