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 language | English |
|---|---|
| Pages (from-to) | 27-34 |
| Number of pages | 8 |
| Journal | Investigational New Drugs |
| Volume | 37 |
| Issue number | 1 |
| DOIs | |
| State | Published - 15 Feb 2019 |
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Keywords
- Cardiomyocytes
- Copper-Tolfenamic acid
- Specificity protein 1
- Survivin
Cite this
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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 journal › Article
TY - JOUR
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
UR - http://www.scopus.com/inward/record.url?scp=85054784576&partnerID=8YFLogxK
U2 - 10.1007/s10637-018-0594-9
DO - 10.1007/s10637-018-0594-9
M3 - Article
C2 - 29761244
AN - SCOPUS:85054784576
VL - 37
SP - 27
EP - 34
JO - Investigational New Drugs
JF - Investigational New Drugs
SN - 0167-6997
IS - 1
ER -