title: Difluorinated-curcumin (CDF): a novel curcumin analog is a potent inhibitor of colon cancer stem-like cells.
abstract: OBJECTIVE
  Recurrence of colon cancer, which affects nearly 50% of patients treated by conventional therapeutics, is thought to be due to re-emergence of chemotherapy-resistant cancer stem/stem-like cells (CSCs). Therefore, development of therapeutic strategies for targeted elimination of CSCs would be a novel strategy. The current study examines whether difluorinated-curcumin (CDF), a novel analog of the dietary ingredient of curcumin, in combination with 5-fluorouracil and oxaliplatin (5-FU + Ox), the mainstay of colon cancer chemotherapeutic, would be effective in eliminating colon CSCs.
  
  
  METHODS
  Multiple methodologies that include real-time RT-PCR, Western blot, MTT assay, caspase-3 activity, colonosphere formation, Hoechst-33342 dye exclusion and NF-κB-ELISA were used.
  
  
  RESULTS
  We observed that CDF together with 5-FU + Ox were more potent than curcumin in reducing CD44 and CD166 in chemo-resistant colon cancer cells, accompanied by inhibition of growth, induction of apoptosis and disintegration of colonospheres. These changes were associated with down-regulation of the membrane transporter ABCG2 and attenuation of EGFR, IGF-1R, and NF-κB signaling consistent with inactivation of β-catenin, COX-2, c-Myc and Bcl-xL and activation of the pro-apoptotic Bax.
  
  
  CONCLUSIONS
  Our results suggest that CDF together with the conventional chemotherapeutics could be an effective treatment strategy for preventing the emergence of chemo-resistant colon cancer cells by eliminating CSCs.
authors.affiliation: Veterans Affairs Medical Center, Wayne State University, Detroit, Michigan 48201, USA.
authors.forename: Shailender Singh
authors.initials: SS
authors.lastname: Kanwar
authors.forename: Yingjie
authors.initials: Y
authors.lastname: Yu
authors.forename: Jyoti
authors.initials: J
authors.lastname: Nautiyal
authors.forename: Bhaumik B
authors.initials: BB
authors.lastname: Patel
authors.forename: Subhash
authors.initials: S
authors.lastname: Padhye
authors.forename: Fazlul H
authors.initials: FH
authors.lastname: Sarkar
authors.forename: Adhip P N
authors.initials: AP
authors.lastname: Majumdar
mesh_terms: D000971:Antineoplastic Combined Chemotherapy Protocols / Q000494:pharmacology*; D017209:Apoptosis / Q000187:drug effects; D015153:Blotting, Western; D049109:Cell Proliferation / Q000187:drug effects; D003110:Colonic Neoplasms / Q000473:pathology; D003474:Curcumin / Q000031:analogs & derivatives* / Q000494:pharmacology; D019008:Drug Resistance, Neoplasm / Q000187:drug effects*; D004357:Drug Synergism; D004797:Enzyme-Linked Immunosorbent Assay; D005466:Fluorocarbons / Q000494:pharmacology; D019073:HT29 Cells; D006801:Humans; D016328:NF-kappa B / Q000378:metabolism; D011485:Protein Binding; D020133:Reverse Transcriptase Polymerase Chain Reaction; D013234:Stem Cells / Q000187:drug effects*
chemical_list: D005466:Fluorocarbons; D016328:NF-kappa B; D003474:Curcumin