The Korean Journal of Physiology and Pharmacology

The Korean Society of Pharmacology (대한약리학회)
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Inhibition of Wnt/β-catenin signaling by monensin in cervical cancer

  • Bingbing Fu (Department of Obstetrics and Gynaecology, Xiangyang Central Hospital, Affiliated Hospital of Hubei University of Arts and Science) ;
  • Lixia Fang (Department of Obstetrics and Gynaecology, Xiangyang Central Hospital, Affiliated Hospital of Hubei University of Arts and Science) ;
  • Ranran Wang (Department of Obstetrics and Gynaecology, Xiangyang Central Hospital, Affiliated Hospital of Hubei University of Arts and Science) ;
  • Xueling Zhang (Department of Obstetrics and Gynaecology, Xiangyang Central Hospital, Affiliated Hospital of Hubei University of Arts and Science)
  • Received : 2023.07.07
  • Accepted : 2023.10.15
  • Published : 2024.01.01
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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.

Keywords

Acknowledgement

This work was supported by a central grant from Xiangyang Central Hospital Research Center Central Grant (CG2019-XJCD65).

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