Niclosamide Exhibits Potent Anticancer Activity and Synergizes with Sorafenib in Human Renal Cell Cancer Cells

Cellular Physiology and Biochemistry : International Journal of Experimental Cellular Physiology, Biochemistry, and Pharmacology
Xinyi YuLiqun Chen

Abstract

As the most lethal urological cancers, renal cell carcinoma (RCC) comprises a heterogeneous group of cancer with diverse genetic and molecular alterations. There is an unmet clinical need to develop efficacious therapeutics for advanced, metastatic and/or relapsed RCC. Here, we investigate whether anthelmintic drug Niclosamide exhibits anticancer activity and synergizes with targeted therapy Sorafenib in suppressing RCC cell proliferation. Cell proliferation and migration were assessed by Crystal violet staining, WST-1 assay, cell wounding and cell cycle analysis. Gene expression was assessed by qPCR. In vivo anticancer activity was assessed in xenograft tumor model. We find that Niclosamide effectively inhibits cell proliferation, cell migration and cell cycle progression, and induces apoptosis in human renal cancer cells. Mechanistically, Niclosamide inhibits the expression of C-MYC and E2F1 while inducing the expression of PTEN in RCC cells. Niclosamide is further shown to synergize with Sorafenib in suppressing RCC cell proliferation and survival. In the xenograft tumor model, Niclosamide is shown to effectively inhibit tumor growth and suppress RCC cell proliferation. Niclosamide may be repurposed as a potent anticancer ag...Continue Reading

Citations

Aug 30, 2019·Cancer Cell International·Yongchang LaiWenqi Wu
Aug 12, 2020·Pharmaceutical Research·Ellen WeisbergJames D Griffin
Mar 4, 2020·International Journal of Oncology·Romina Gabriela ArmandoDaniel Eduardo Gomez
Jun 18, 2021·Pharmacological Research : the Official Journal of the Italian Pharmacological Society·Yu HeShufang Liang
Jul 3, 2021·Cancers·Christina PfabNahed El-Najjar

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