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Difluorinated-Curcumin (CDF): A Novel Curcumin Analog is a Potent Inhibitor of Colon Cancer Stem-Like Cells

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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.

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ACKNOWLEDGMENTS

This work was supported by grants from the National Institutes of Health/National Institute on Aging (5RO1 AG014343) and the Department of Veterans Affairs (A.P.N.M.) and from the National Cancer Institute, NIH (3RO1 CA131151-02) (F.H.S).

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Authors and Affiliations

  1. Veterans Affairs Medical Center, Wayne State University, Detroit, Michigan, 48201, USA

    Shailender Singh Kanwar, Yingjie Yu, Jyoti Nautiyal, Bhaumik B. Patel & Adhip P. N. Majumdar

  2. Department of Internal Medicine, Wayne State University, Detroit, Michigan, 48201, USA

    Shailender Singh Kanwar, Yingjie Yu, Jyoti Nautiyal, Bhaumik B. Patel, Fazlul H. Sarkar & Adhip P. N. Majumdar

  3. Department of Pathology, Detroit, Michigan, 48201, USA

    Jyoti Nautiyal & Fazlul H. Sarkar

  4. Karmanos Cancer Institute, Wayne State University, Detroit, Michigan, 48201, USA

    Bhaumik B. Patel, Fazlul H. Sarkar & Adhip P. N. Majumdar

  5. Dr. D.Y. Patil University, Pune, 411018, India

    Subhash Padhye

  6. VA Medical Center, Research Service, 4646 John R; Room-B4238, Detroit, Michigan, 48201, USA

    Adhip P. N. Majumdar

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  1. Shailender Singh Kanwar
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Correspondence to Adhip P. N. Majumdar.

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Kanwar, S.S., Yu, Y., Nautiyal, J. et al. Difluorinated-Curcumin (CDF): A Novel Curcumin Analog is a Potent Inhibitor of Colon Cancer Stem-Like Cells. Pharm Res 28, 827–838 (2011). https://doi.org/10.1007/s11095-010-0336-y

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  • DOI: https://doi.org/10.1007/s11095-010-0336-y

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