title: Omega-3 eicosapentaenoic acid decreases CD133 colon cancer stem-like cell marker expression while increasing sensitivity to chemotherapy.
abstract: Colorectal cancer is the third leading cause of cancer-related death in the western world. In vitro and in vivo experiments showed that omega-3 polyunsaturated fatty acids (n-3 PUFAs) can attenuate the proliferation of cancer cells, including colon cancer, and increase the efficacy of various anticancer drugs. However, these studies address the effects of n-3 PUFAs on the bulk of the tumor cells and not on the undifferentiated colon cancer stem-like cells (CSLCs) that are responsible for tumor formation and maintenance. CSLCs have also been linked to the acquisition of chemotherapy resistance and to tumor relapse. Colon CSLCs have been immunophenotyped using several antibodies against cellular markers including CD133, CD44, EpCAM, and ALDH. Anti-CD133 has been used to isolate a population of colon cancer cells that retains stem cells properties (CSLCs) from both established cell lines and primary cell cultures. We demonstrated that the n-3 PUFA, eicosapentaenoic acid (EPA), was actively incorporated into the membrane lipids of COLO 320 DM cells. 25 uM EPA decreased the cell number of the overall population of cancer cells, but not of the CD133 (+) CSLCs. Also, we observed that EPA induced down-regulation of CD133 expression and up-regulation of colonic epithelium differentiation markers, Cytokeratin 20 (CK20) and Mucin 2 (MUC2). Finally, we demonstrated that EPA increased the sensitivity of COLO 320 DM cells (total population) to both standard-of-care chemotherapies (5-Fluorouracil and oxaliplatin), whereas EPA increased the sensitivity of the CD133 (+) CSLCs to only 5-Fluorouracil.
authors.affiliation: Department of Biochemistry and Microbiology, Joan Edwards School of Medicine, Marshall University, Huntington, West Virginia, United States of America.
authors.forename: Flavia
authors.initials: F
authors.lastname: De Carlo
authors.forename: Theodore R
authors.initials: TR
authors.lastname: Witte
authors.forename: W Elaine
authors.initials: WE
authors.lastname: Hardman
authors.forename: Pier Paolo
authors.initials: PP
authors.lastname: Claudio
mesh_terms: D000071916:AC133 Antigen; D015703:Antigens, CD / Q000378:metabolism*; D000970:Antineoplastic Agents / Q000494:pharmacology*; D045744:Cell Line, Tumor; D049109:Cell Proliferation / Q000187:drug effects; D015118:Eicosapentaenoic Acid / Q000494:pharmacology*; D005472:Fluorouracil / Q000494:pharmacology; D006023:Glycoproteins / Q000378:metabolism*; D006801:Humans; D014411:Neoplastic Stem Cells / Q000187:drug effects* / Q000378:metabolism*; D009944:Organoplatinum Compounds / Q000494:pharmacology; D000077150:Oxaliplatin; D010455:Peptides / Q000378:metabolism*
chemical_list: D000071916:AC133 Antigen; D015703:Antigens, CD; D000970:Antineoplastic Agents; D006023:Glycoproteins; D009944:Organoplatinum Compounds; C000606023:PROM1 protein, human; D010455:Peptides; D000077150:Oxaliplatin; D015118:Eicosapentaenoic Acid; D005472:Fluorouracil