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Author Notes:

Correspondence to: Riyaz Basha, e-mail: Riyaz.Bahsa@unthsc.edu, riyazbasha@yahoo.com.

The authors thank Anthea Hammond (Technical Writer, Emory University) for editing of the manuscript.

The authors declare they have no conflicts of interests.

Subjects:

Research Funding:

This work is partially supported by the funds from the Institute for Cancer Research (RB), Precilincal Services (JWS), UNT Health Science Center, Fort Worth, TX.

Keywords:

  • Life Sciences & Biomedicine
  • Oncology
  • Cell Biology
  • colon cancer
  • tolfenamic acid
  • curcumin
  • Sp1
  • NF-kB
  • I CLINICAL-TRIAL
  • NF-KAPPA-B
  • PANCREATIC-CANCER
  • TUMOR-GROWTH
  • DOWN-REGULATION
  • SURVIVIN GENE
  • EXPRESSION
  • ANTICANCER
  • ANGIOGENESIS
  • CELECOXIB

Combination of Tolfenamic acid and curcumin induces colon cancer cell growth inhibition through modulating specific transcription factors and reactive oxygen species

Tools:

Journal Title:

Oncotarget

Volume:

Volume 7, Number 3

Publisher:

, Pages 3186-3200

Type of Work:

Article | Final Publisher PDF

Abstract:

Curcumin (Cur) has been extensively studied in several types of malignancies including colorectal cancer (CRC); however its clinical application is greatly affected by low bioavailability. Several strategies to improve the therapeutic response of Cur are being pursued, including its combination with small molecules and drugs. We investigated the therapeutic efficacy of Cur in combination with the small molecule tolfenamic acid (TA) in CRC cell lines. TA has been shown to inhibit the growth of human cancer cells in vitro and in vivo, via targeting the transcription factor specificity protein1 (Sp1) and suppressing survivin expression. CRC cell lines HCT116 and HT29 were treated with TA and/or Cur and cell viability was measured 24-72 hours post-treatment. While both agents caused a steady reduction in cell viability, following a clear dose/time-dependent response, the combination of TA+Cur showed higher growth inhibition when compared to either single agent. Effects on apoptosis were determined using flow cytometry (JC-1 staining to measure mitochondrial membrane potential), Western blot analysis (c-PARP expression) and caspase 3/7 activity. Reactive oxygen species (ROS) levels were measured by flow cytometry and the translocation of NF-kB into the nucleus was determined using immunofluorescence. Results showed that apoptotic markers and ROS activity were significantly upregulated following combination treatment, when compared to the individual agents. This was accompanied by decreased expression of Sp1, survivin and NF-kB translocation. The combination of TA+Cur was more effective in HCT116 cells than HT29 cells. These results demonstrate that TA may enhance the anti-proliferative efficacy of Cur in CRC cells.

Copyright information:

© 2016 Sankpal et al.

This is an Open Access work distributed under the terms of the Creative Commons Attribution 3.0 Unported License (http://creativecommons.org/licenses/by/3.0/).

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