Nigericin Exerts Anticancer Effects on Human Colorectal Cancer Cells by Inhibiting Wnt/β-catenin Signaling Pathway

Molecular Cancer Therapeutics
Fei LiuQiaoming Zhi

Abstract

Nigericin, an antibiotic derived from Streptomyces hygroscopicus, which works by acting as an H+, K+, and Pb2+ ionophore, has exhibited promising anticancer activity. The main purpose of this study is to investigate its inhibitory effects on Wnt/β-catenin signaling pathway in colorectal cancer cells and clarify the underlying mechanism. We exposed two colorectal cancer lines (SW620 and KM12) to increasing concentrations of nigericin for different time periods and the 50% inhibiting concentration (IC50) values were evaluated. Our data showed that nigericin treatment significantly reduced tumor cell proliferation in dose- and time-dependent manners in colorectal cancer cells. The subsequent experiments in vitro and in vivo implied that nigericin could significantly suppress the tumor growth, migration, and invasion, and induce the apoptosis of colorectal cancer cells. Our results of Western blot and immunofluorescence assay showed that nigericin could suppress the Wnt/β-catenin signaling pathway in colorectal cancer cells with dose-dependent increased expressions of downstream effectors and target proteins. To further elucidate the inhibitory effects of nigericin via a β-catenin-dependent signaling mechanism, we established the s...Continue Reading

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Feb 23, 2021·Frontiers in Immunology·Gulcin TezcanSvetlana F Khaiboullina

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