Difluorinated-curcumin (CDF): a novel curcumin analog is a potent inhibitor of colon cancer stem-like cells.

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 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: Shailender Singh Kanwar, Yingjie Yu, Jyoti Nautiyal, Bhaumik B Patel, Subhash Padhye, Fazlul H Sarkar, Adhip P N Majumdar
• Journal: Pharmaceutical research (Pharm Res) Vol. 28 Issue 4 Pg. 827-38 (Apr 2011) ISSN: 1573-904X [Electronic] United States
• PMID: 21161336 (Publication Type: Journal Article, Research Support, N.I.H., Extramural, Research Support, U.S. Gov't, Non-P.H.S.)

Chemical References

• Fluorocarbons
• NF-kappa B
• Curcumin

Topics

• Antineoplastic Combined Chemotherapy Protocols (pharmacology)
• Apoptosis (drug effects)
• Blotting, Western
• Cell Proliferation (drug effects)
• Colonic Neoplasms (pathology)
• Curcumin (analogs & derivatives, pharmacology)
• Drug Resistance, Neoplasm (drug effects)
• Drug Synergism
• Enzyme-Linked Immunosorbent Assay
• Fluorocarbons (pharmacology)
• HT29 Cells
• Humans
• NF-kappa B (metabolism)
• Protein Binding
• Reverse Transcriptase Polymerase Chain Reaction
• Stem Cells (drug effects)