TY - JOUR
T1 - Fluorinated N,N'-diarylureas as novel therapeutic agents against cancer stem cells
AU - Kenlan, Dasha E.
AU - Rychahou, Piotr
AU - Sviripa, Vitaliy M.
AU - Weiss, Heidi L.
AU - Liu, Chunming
AU - Watt, David S.
AU - Evers, B. Mark
N1 - Publisher Copyright:
© 2017 AACR.
PY - 2017/5/1
Y1 - 2017/5/1
N2 - 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.
AB - 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.
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UR - http://www.scopus.com/inward/citedby.url?scp=85020189452&partnerID=8YFLogxK
U2 - 10.1158/1535-7163.MCT-15-0634
DO - 10.1158/1535-7163.MCT-15-0634
M3 - Article
C2 - 28258165
AN - SCOPUS:85020189452
SN - 1535-7163
VL - 16
SP - 831
EP - 837
JO - Molecular Cancer Therapeutics
JF - Molecular Cancer Therapeutics
IS - 5
ER -
