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Pharmaceutical Research

, Volume 28, Issue 4, pp 827–838 | Cite as

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

  • Shailender Singh Kanwar
  • Yingjie Yu
  • Jyoti Nautiyal
  • Bhaumik B. Patel
  • Subhash Padhye
  • Fazlul H. Sarkar
  • Adhip P. N. Majumdar
Research Paper

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.

KEY WORDS

β-catenin chemo-resistance NF-κB oxaliplatin 5-fluorouracil 

Notes

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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Copyright information

© Springer Science+Business Media, LLC 2010

Authors and Affiliations

  • Shailender Singh Kanwar
    • 1
    • 2
  • Yingjie Yu
    • 1
    • 2
  • Jyoti Nautiyal
    • 1
    • 2
    • 3
  • Bhaumik B. Patel
    • 1
    • 2
    • 4
  • Subhash Padhye
    • 5
  • Fazlul H. Sarkar
    • 2
    • 3
    • 4
  • Adhip P. N. Majumdar
    • 1
    • 2
    • 4
    • 6
  1. 1.Veterans Affairs Medical CenterWayne State UniversityDetroitUSA
  2. 2.Department of Internal MedicineWayne State UniversityDetroitUSA
  3. 3.Department of PathologyDetroitUSA
  4. 4.Karmanos Cancer InstituteWayne State UniversityDetroitUSA
  5. 5.Dr. D.Y. Patil UniversityPuneIndia
  6. 6.VA Medical CenterResearch ServiceDetroitUSA

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