Inhibition of Wnt/β-catenin signaling by monensin in cervical cancer

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 in-volved 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 treat-ment. In conclusion, our findings provide pre-clinical evidence that supports further exploration of monensin's potential for repurposing in cervical cancer therapy, par - ticularly for patients exhibiting aberrant Wnt/ β -catenin activation