TY - JOUR
T1 - Copper-tolfenamic acid
T2 - evaluation of stability and anti-cancer activity
AU - Hurtado, Myrna
AU - Sankpal, Umesh T.
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
N1 - Funding Information:
Authors thank the Children’s Oncology Group (COG) for freely providing the Ewing sarcoma cell lines, CHLA10 and TC205. Authors also acknowledge the technical assistance of Ms. Lina Albeer for culturing COG cell lines.
Funding Information:
Funding Some of the research presented in this manuscript is partially supported by a grant from the Shirley E. Noland Foundation, Melbourne, FL, USA awarded to RB. UTS and RB are supported by a grant (# 2 U54 MD006882–06) from the National Institutes of Minority Health and Health Disparities. RM is supported by an International Fellowship from the Indian Council of Medical Research.
Publisher Copyright:
© 2018, Springer Science+Business Media, LLC, part of Springer Nature.
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 -