Tolfenamic acid-induced alterations in genes and pathways in pancreatic cancer cells

Umesh T. Sankpal, Steven Goodison, Michelle Jones-Pauley, Myrna Hurtado, Fan Zhang, Riyaz Basha

Research output: Contribution to journalArticle

5 Citations (Scopus)

Abstract

Non-steroidal anti-inflammatory drugs (NSAIDs) are being tested extensively for their role in the treatment and prevention of several cancers. Typically NSAIDs exhibit anti-tumor activities via modulation of cyclooxygenase (COX)-dependent mechanisms, however, an anti-cancer NSAID tolfenamic acid (TA) is believed to work through COXindependent pathways. Results from our laboratory and others have demonstrated the anti-cancer activity of TA in various cancer models including pancreatic cancer. TA has been shown to modulate certain cellular processes including, apoptosis, reactive oxygen species and signaling. In this study, molecular profiling was performed to precisely understand the mode of action of TA. Three pancreatic cancer cell lines, L3.6pl, MIA PaCa-2, and Panc1 were treated with TA (50 μM for 48 h) and the changes in gene expression was evaluated using the Affymetrix GeneChip Human Gene ST Array platform. Microarray results were further validated using quantitative PCR for seven genes altered by TA treatment in all three cell lines. Functional analysis of differentially expressed genes (2 fold increase or decrease, p < 0.05) using Ingenuity Pathway Analysis software, revealed that TA treatment predominantly affected the genes involved in cell cycle, cell growth and proliferation, and cell death and survival. Promoter analysis of the differentially expressed genes revealed that they are enriched for Sp1 binding sites, suggesting that Sp1 could be a major contributor in mediating the effect of TA. The gene expression studies identified new targets involved in TA's mode of action, while supporting the hypothesis about the association of Sp1 in TA mediated effects in pancreatic cancer.

Original languageEnglish (US)
Pages (from-to)14593-14603
Number of pages11
JournalOncotarget
Volume8
Issue number9
DOIs
StatePublished - Jan 1 2017

Fingerprint

Pancreatic Neoplasms
Genes
Anti-Inflammatory Agents
Neoplasms
Pharmaceutical Preparations
Gene Expression
tolfenamic acid
Cell Line
Prostaglandin-Endoperoxide Synthases
Reactive Oxygen Species
Cell Survival
Cell Cycle
Cell Death
Software
Binding Sites
Cell Proliferation
Apoptosis
Polymerase Chain Reaction
Growth

Keywords

  • Microarray analysis
  • Pancreatic cancer
  • Sp1
  • Tolfenamic acid

ASJC Scopus subject areas

  • Oncology

Cite this

Sankpal, U. T., Goodison, S., Jones-Pauley, M., Hurtado, M., Zhang, F., & Basha, R. (2017). Tolfenamic acid-induced alterations in genes and pathways in pancreatic cancer cells. Oncotarget, 8(9), 14593-14603. https://doi.org/10.18632/oncotarget.14651

Tolfenamic acid-induced alterations in genes and pathways in pancreatic cancer cells. / Sankpal, Umesh T.; Goodison, Steven; Jones-Pauley, Michelle; Hurtado, Myrna; Zhang, Fan; Basha, Riyaz.

In: Oncotarget, Vol. 8, No. 9, 01.01.2017, p. 14593-14603.

Research output: Contribution to journalArticle

Sankpal, UT, Goodison, S, Jones-Pauley, M, Hurtado, M, Zhang, F & Basha, R 2017, 'Tolfenamic acid-induced alterations in genes and pathways in pancreatic cancer cells', Oncotarget, vol. 8, no. 9, pp. 14593-14603. https://doi.org/10.18632/oncotarget.14651
Sankpal, Umesh T. ; Goodison, Steven ; Jones-Pauley, Michelle ; Hurtado, Myrna ; Zhang, Fan ; Basha, Riyaz. / Tolfenamic acid-induced alterations in genes and pathways in pancreatic cancer cells. In: Oncotarget. 2017 ; Vol. 8, No. 9. pp. 14593-14603.
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