Copper-tolfenamic acid: evaluation of stability and anti-cancer activity

Myrna Hurtado, Umesh T. Sankpal, Jaya Chhabra, Deondra T. Brown, Rajasekhar Maram, Rafid Patel, Raj K. Gurung, Jerry Simecka, Alvin A. Holder, Riyaz Basha

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Abstract

The non-steroidal anti-inflammatory drug, Tolfenamic acid (TA) acts as an anti-cancer agent in several adult and pediatric cancer models. Copper (Cu) is an important element with multiple biological functions and has gained interest in medical applications. Recently, [Cu(TA) 2 (bpy)] (Cu-TA) has been synthesized in order to enhance therapeutic activity. In this study, we synthesized Cu-TA using an established method, characterized it by UV visible spectroscopy and Fourier-transform infrared spectroscopy (FTIR), and tested its anti-cancer activity using twelve cell lines representing various cancers, such as Ewing sarcoma, glioblastoma, medulloblastoma, neuroblastoma, pancreatic and prostate. The anti-proliferative activity of Cu-TA was determined at 48 h post-treatment and compared with the parental compound, TA. The IC 50 values were calculated using GraphPad Prism software. The biological stability of Cu-TA was evaluated using twelve-month-old powder and six-month-old stock solution. Cardiomyocytes (H9C2) were used to test the cytotoxicity in non-malignant cells. Cu-TA showed higher anti-proliferative activity, and the IC 50 values were 30 to 80% lower when compared with TA. H9C2 cells were non-responsive to Cu-TA, suggesting that it is selective towards malignant cells. Comparison of the twelve-month-old powder and six-month-old stock solution using the Panc1 cell line showed similar IC 50 values (<5% variation), confirming the stability of Cu-TA either in powder or solution form. These findings demonstrate the potential of Cu-TA as an effective anti-cancer agent. Further studies to delineate the detailed mechanism of action of Cu-TA for specific cancer model are underway.

Original languageEnglish
Pages (from-to)27-34
Number of pages8
JournalInvestigational New Drugs
Volume37
Issue number1
DOIs
Publication statusPublished - 15 Feb 2019

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Keywords

  • Cardiomyocytes
  • Copper-Tolfenamic acid
  • Specificity protein 1
  • Survivin

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