Fluorinated NN′-Diarylureas As Novel Therapeutic Agents Against Cancer Stem Cells

摘要

Colorectal cancer (CRC) is the second-leading cause of cancer-related mortality in the United States. Over 50% of patients with CRC will develop local recurrence or distant organ metastasis. Cancer stem cells play a major role in the survival and metastasis of cancer cells. In this study, we examined the effects of novel AMP-activated protein kinase (AMPK) activating compounds on CRC metastatic and stem cell lines as potential candidates for chemotherapy. We found that activation of AMPK by all fluorinated N,N-diarylureas (FND) compounds at micromolar levels significantly inhibited the cell cycle progression and subsequent cellular proliferation. Additionally, we demonstrated that select FNDs significantly increased apoptosis in CRC metastatic and cancer stem cells. Therefore, FNDs hold considerable promise in the treatment of metastatic CRC, through elimination of both regular cancer cells and cancer stem cells.