title: Fluorinated N,N'-Diarylureas As Novel Therapeutic Agents Against Cancer Stem Cells.
abstract: 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.Mol Cancer Ther; 16(5); 831-7. ©2017 AACR.
authors.affiliation: Lucille Parker Markey Cancer Center, University of Kentucky, Lexington, Kentucky.
authors.forename: Dasha E
authors.initials: DE
authors.lastname: Kenlan
authors.affiliation: Lucille Parker Markey Cancer Center, University of Kentucky, Lexington, Kentucky.|Department of Surgery, University of Kentucky, Lexington, Kentucky.
authors.forename: Piotr
authors.initials: P
authors.lastname: Rychahou
authors.affiliation: Department of Molecular and Cellular Biochemistry, University of Kentucky, Lexington, Kentucky.
authors.forename: Vitaliy M
authors.initials: VM
authors.lastname: Sviripa
authors.affiliation: Lucille Parker Markey Cancer Center, University of Kentucky, Lexington, Kentucky.
authors.forename: Heidi L
authors.initials: HL
authors.lastname: Weiss
authors.affiliation: Department of Molecular and Cellular Biochemistry, University of Kentucky, Lexington, Kentucky.
authors.forename: Chunming
authors.initials: C
authors.lastname: Liu
authors.affiliation: Department of Molecular and Cellular Biochemistry, University of Kentucky, Lexington, Kentucky.
authors.forename: David S
authors.initials: DS
authors.lastname: Watt
authors.affiliation: Lucille Parker Markey Cancer Center, University of Kentucky, Lexington, Kentucky. mark.evers@uky.edu.|Department of Surgery, University of Kentucky, Lexington, Kentucky.
authors.forename: B Mark
authors.initials: BM
authors.lastname: Evers
mesh_terms: D000091162:AMP-Activated Protein Kinase Kinases; D017209:Apoptosis / Q000187:drug effects; D045744:Cell Line, Tumor; D049109:Cell Proliferation / Q000187:drug effects; D015179:Colorectal Neoplasms / Q000188:drug therapy* / Q000235:genetics / Q000473:pathology; D004789:Enzyme Activation / Q000187:drug effects*; D015972:Gene Expression Regulation, Neoplastic / Q000187:drug effects; D054879:Halogenation; D006801:Humans; D009362:Neoplasm Metastasis; D009364:Neoplasm Recurrence, Local / Q000188:drug therapy* / Q000235:genetics / Q000473:pathology; D014411:Neoplastic Stem Cells / Q000187:drug effects* / Q000473:pathology; D010766:Phosphorylation; D011494:Protein Kinases / Q000378:metabolism*
chemical_list: D011494:Protein Kinases; D000091162:AMP-Activated Protein Kinase Kinases