caa a22 4500 445313285 CHVBK 20180317142637.0 cr unu---uuuuu 170323e20110401xx s 000 0 eng 10.1007/s11095-010-0336-y doi (NATIONALLICENCE)springer-10.1007/s11095-010-0336-y Difluorinated-Curcumin (CDF): A Novel Curcumin Analog is a Potent Inhibitor of Colon Cancer Stem-Like Cells [Elektronische Daten] [Shailender Kanwar, Yingjie Yu, Jyoti Nautiyal, Bhaumik Patel, Subhash Padhye, Fazlul Sarkar, Adhip Majumdar] ABSTRACT: Purpose: 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 diflourinated-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. Springer Science+Business Media, LLC, 2010 β-catenin nationallicence chemo-resistance nationallicence NF-κB nationallicence oxaliplatin nationallicence 5-fluorouracil nationallicence Kanwar Shailender Veterans Affairs Medical Center, Wayne State University, 48201, Detroit, Michigan, USA aut Yu Yingjie Veterans Affairs Medical Center, Wayne State University, 48201, Detroit, Michigan, USA aut Nautiyal Jyoti Veterans Affairs Medical Center, Wayne State University, 48201, Detroit, Michigan, USA aut Patel Bhaumik Veterans Affairs Medical Center, Wayne State University, 48201, Detroit, Michigan, USA aut Padhye Subhash Dr. D.Y. Patil University, 411018, Pune, India aut Sarkar Fazlul Department of Internal Medicine, Wayne State University, 48201, Detroit, Michigan, USA aut Majumdar Adhip Veterans Affairs Medical Center, Wayne State University, 48201, Detroit, Michigan, USA aut Pharmaceutical Research Springer US; http://www.springer-ny.com 28/4(2011-04-01), 827-838 0724-8741 28:4<827 2011 28 11095 https://doi.org/10.1007/s11095-010-0336-y text/html Onlinezugriff via DOI 1 research-article jats NATIONALLICENCE 856 40 https://doi.org/10.1007/s11095-010-0336-y text/html Onlinezugriff via DOI NATIONALLICENCE 700 1- Kanwar Shailender Veterans Affairs Medical Center, Wayne State University, 48201, Detroit, Michigan, USA aut NATIONALLICENCE 700 1- Yu Yingjie Veterans Affairs Medical Center, Wayne State University, 48201, Detroit, Michigan, USA aut NATIONALLICENCE 700 1- Nautiyal Jyoti Veterans Affairs Medical Center, Wayne State University, 48201, Detroit, Michigan, USA aut NATIONALLICENCE 700 1- Patel Bhaumik Veterans Affairs Medical Center, Wayne State University, 48201, Detroit, Michigan, USA aut NATIONALLICENCE 700 1- Padhye Subhash Dr. D.Y. Patil University, 411018, Pune, India aut NATIONALLICENCE 700 1- Sarkar Fazlul Department of Internal Medicine, Wayne State University, 48201, Detroit, Michigan, USA aut NATIONALLICENCE 700 1- Majumdar Adhip Veterans Affairs Medical Center, Wayne State University, 48201, Detroit, Michigan, USA aut NATIONALLICENCE 773 0- Pharmaceutical Research Springer US; http://www.springer-ny.com 28/4(2011-04-01), 827-838 0724-8741 28:4<827 2011 28 11095 Metadata rights reserved Springer special CC-BY-NC licence nationallicence BK010053 XK010053 XK010000 NATIONALLICENCE NATIONALLICENCE NL-springer