Colorectal cancer is the second-leading cause of cancer-related mortality in the United States. More than 50% of patients with colorectal cancer 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 colorectal cancer 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. In addition, we demonstrated that select FNDs significantly increased apoptosis in colorectal cancer metastatic and cancer stem cells. Therefore, FNDs hold considerable promise in the treatment of metastatic colorectal cancer, through elimination of both regular cancer cells and cancer stem cells.
Digital Object Identifier (DOI)
NCI P30 CA177558 (to B.M. Evers), NCATS UL1TR000117 (to B.M. Evers), R01 DK048498 (to B.M. Evers), Markey Cancer Foundation (to B.M. Evers), NIH R21 CA139359 (to C. Liu and D.S. Watt), NIH R01 CA172379 (to C. Liu and D.S. Watt), Office of the Dean of the College of Medicine (to D.S. Watt), NIH P20 RR020171 (to D.S. Watt).
Kenlan, Dasha E.; Rychahou, Piotr G.; Sviripa, Vitaliy M.; Weiss, Heidi L.; Liu, Chunming; Watt, David S.; and Evers, B. Mark, "Fluorinated N,N'-Diarylureas as Novel Therapeutic Agents Against Cancer Stem Cells" (2017). Markey Cancer Center Faculty Publications. 131.