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

• 발행기관: 대한생리학회-대한약리학회
• 저자명: Fu Bingbing Fang Lixia Wang Ranran Zhang Xueling
• 간행물 정보: 『The Korean Journal of Physiology & Pharmacology』제28권 제1호, 21~30쪽, 전체 10쪽
• 주제분류: 의약학 > 의학일반
• 파일형태: PDF
• 발행일자: 2024.01.31

국문 초록

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

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키워드

Monensin Oxidative stress Uterine cervical neoplasms Wnt beta-catenin signaling pathway