Medicinal Chemistry

Identification of Niclosamide as a New Lead Compound to Suppress the Metastasis of Prostate Cancer Cells

Abstract

Xiaomei Ren, Zhang Zhang, Lei Duan and Ke Ding

Prostate cancer is one of the most common cancer types among males. Metastasis in advanced stages of prostate cancer makes the disease refractory to current treatments and is the leading cause of death of advanced prostate cancer. Drugs targeting metastasis may provide new therapeutic strategies for advanced prostate cancer. We identified the traditional antihelminthic drug niclosamide to have great potential in suppressing the metastatic process of prostate cancer. The drug potently inhibited the migration and invasion of the DU145 prostate cancer cell line. It significantly suppressed the protein levels of key members of the matrix metalloproteinase family (MMP2 and MMP9), as well as cadherins and catenins (E-/N-cadherin and β-catenin), all of which are critical factors in the metastastic process. Further investigation suggested that the motility inhibition of niclosamide on DU145 cells was highly correlated to its suppression of the STAT3 and MAPK signaling pathways.