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

Umesh T. Sankpal, Ganji Purnachandra Nagaraju, Sriharika R. Gottipolu, Myrna Hurtado, Christopher G. Jordan, Jerry W. Simecka, Mamoru Shoji, Bassel El-Rayes, Riyaz Basha

Research output: Contribution to journalArticle

31 Citations (Scopus)

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.

Original languageEnglish
Pages (from-to)3186-3200
Number of pages15
JournalOncotarget
Volume7
Issue number3
DOIs
StatePublished - 1 Jan 2016

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Curcumin
Colonic Neoplasms
Reactive Oxygen Species
Transcription Factors
Growth
Colorectal Neoplasms
NF-kappa B
Cell Survival
Flow Cytometry
HCT116 Cells
Caspase 7
Cell Line
HT29 Cells
Mitochondrial Membrane Potential
Therapeutics
tolfenamic acid
Caspase 3
Biological Availability
Fluorescent Antibody Technique
Neoplasms

Keywords

  • Colon cancer
  • Curcumin
  • NF-kB
  • Sp1
  • Tolfenamic acid

Cite this

Sankpal, Umesh T. ; Nagaraju, Ganji Purnachandra ; Gottipolu, Sriharika R. ; Hurtado, Myrna ; Jordan, Christopher G. ; Simecka, Jerry W. ; Shoji, Mamoru ; El-Rayes, Bassel ; Basha, Riyaz. / Combination of Tolfenamic acid and curcumin induces colon cancer cell growth inhibition through modulating specific transcription factors and reactive oxygen species. In: Oncotarget. 2016 ; Vol. 7, No. 3. pp. 3186-3200.
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Combination of Tolfenamic acid and curcumin induces colon cancer cell growth inhibition through modulating specific transcription factors and reactive oxygen species. / Sankpal, Umesh T.; Nagaraju, Ganji Purnachandra; Gottipolu, Sriharika R.; Hurtado, Myrna; Jordan, Christopher G.; Simecka, Jerry W.; Shoji, Mamoru; El-Rayes, Bassel; Basha, Riyaz.

In: Oncotarget, Vol. 7, No. 3, 01.01.2016, p. 3186-3200.

Research output: Contribution to journalArticle

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