Copper-tolfenamic acid

evaluation of stability and anti-cancer activity

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

Research output: Contribution to journalArticleResearchpeer-review

1 Citation (Scopus)

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
StatePublished - 15 Feb 2019

Fingerprint

Copper
Neoplasms
Powders
tolfenamic acid
Cell Line
Medulloblastoma
Ewing's Sarcoma
Fourier Transform Infrared Spectroscopy
Glioblastoma
Neuroblastoma
Cardiac Myocytes
Prostate
Spectrum Analysis
Anti-Inflammatory Agents
Software
Pediatrics

Keywords

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

Cite this

Hurtado, Myrna ; Sankpal, Umesh Tanaji ; Chhabra, Jaya ; Brown, Deondra T. ; Maram, Rajasekhar ; Patel, Rafid ; Gurung, Raj K. ; Simecka, Jerry ; Holder, Alvin A. ; Basha, Riyaz Mahammad. / Copper-tolfenamic acid : evaluation of stability and anti-cancer activity. In: Investigational New Drugs. 2019 ; Vol. 37, No. 1. pp. 27-34.
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title = "Copper-tolfenamic acid: evaluation of stability and anti-cancer activity",
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.",
keywords = "Cardiomyocytes, Copper-Tolfenamic acid, Specificity protein 1, Survivin",
author = "Myrna Hurtado and Sankpal, {Umesh Tanaji} and Jaya Chhabra and Brown, {Deondra T.} and Rajasekhar Maram and Rafid Patel and Gurung, {Raj K.} and Jerry Simecka and Holder, {Alvin A.} and Basha, {Riyaz Mahammad}",
year = "2019",
month = "2",
day = "15",
doi = "10.1007/s10637-018-0594-9",
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Hurtado, M, Sankpal, UT, Chhabra, J, Brown, DT, Maram, R, Patel, R, Gurung, RK, Simecka, J, Holder, AA & Basha, RM 2019, 'Copper-tolfenamic acid: evaluation of stability and anti-cancer activity', Investigational New Drugs, vol. 37, no. 1, pp. 27-34. https://doi.org/10.1007/s10637-018-0594-9

Copper-tolfenamic acid : evaluation of stability and anti-cancer activity. / Hurtado, Myrna; Sankpal, Umesh Tanaji; Chhabra, Jaya; Brown, Deondra T.; Maram, Rajasekhar; Patel, Rafid; Gurung, Raj K.; Simecka, Jerry; Holder, Alvin A.; Basha, Riyaz Mahammad.

In: Investigational New Drugs, Vol. 37, No. 1, 15.02.2019, p. 27-34.

Research output: Contribution to journalArticleResearchpeer-review

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T1 - Copper-tolfenamic acid

T2 - evaluation of stability and anti-cancer activity

AU - Hurtado, Myrna

AU - Sankpal, Umesh Tanaji

AU - Chhabra, Jaya

AU - Brown, Deondra T.

AU - Maram, Rajasekhar

AU - Patel, Rafid

AU - Gurung, Raj K.

AU - Simecka, Jerry

AU - Holder, Alvin A.

AU - Basha, Riyaz Mahammad

PY - 2019/2/15

Y1 - 2019/2/15

N2 - 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.

AB - 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.

KW - Cardiomyocytes

KW - Copper-Tolfenamic acid

KW - Specificity protein 1

KW - Survivin

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