Anti-leukemic response of a NSAID, tolfenamic acid

Robert M. Sutphin, Sarah F. Connelly, Chris M. Lee, Umesh Tanaji Sankpal, Don Eslin, Moeez Khan, Hima Pius, Riyaz Mahammad Basha

Research output: Contribution to journalArticle

6 Citations (Scopus)

Abstract

Tolfenamic acid (TA), a non-steroidal anti-inflammatory drug, is known to inhibit human cancer cells and mouse tumor growth in some cancer models; however, its anti-leukemic response has not been evaluated. TA targets specificity protein (Sp) transcription factors that mediate the expression of several genes associated with cancer including survivin, a key member of inhibitor of apoptosis protein family. Our aim was to test the anti-leukemic efficacy of TA in pre-clinical experiments. The anti-leukemic response of TA was determined using Jurkat and Nalm-6 cell lines. Cells were treated with increasing (25/50/75 μM) concentrations of TA, and cell viability was measured at 24, 48, and 72 h post-treatment. TA showed a steady and consistent decrease in cell viability following a clear dose and time dependent response. Apoptosis and cell cycle analysis was performed using flow cytometry. Results showed a significant increase in the apoptotic fraction (annexin V positive) following TA treatment, while cell cycle phase distribution analysis showed G0/G1 arrest. TA-induced apoptosis was further confirmed by examining the activation of caspase 3/7 and the expression of cleaved PARP. TA modulated the expression of critical candidates associated with the early phases of cell cycle and validated its efficacy in causing G0/G 1 arrest. The Western blot results revealed that TA significantly decreases Sp1 and survivin expression. These results demonstrate that the anti-leukemic response of TA occurs potentially through targeting Sp1 and inhibiting survivin and suggest the efficacy of TA as a novel therapeutic agent for leukemia.

Original languageEnglish
Pages (from-to)135-144
Number of pages10
JournalTargeted Oncology
Volume9
Issue number2
DOIs
StatePublished - 1 Jan 2014

Fingerprint

Non-Steroidal Anti-Inflammatory Agents
Cell Cycle
tolfenamic acid
Neoplasms
Cell Survival
Sp Transcription Factors
Apoptosis
Inhibitor of Apoptosis Proteins
Caspase 7
Annexin A5
Caspase 3
Flow Cytometry
Leukemia
Anti-Inflammatory Agents
Western Blotting
Gene Expression

Keywords

  • Leukemia
  • NSAID
  • Sp1
  • Survivin
  • Tolfenamic acid
  • Transcription factors

Cite this

Sutphin, Robert M. ; Connelly, Sarah F. ; Lee, Chris M. ; Sankpal, Umesh Tanaji ; Eslin, Don ; Khan, Moeez ; Pius, Hima ; Basha, Riyaz Mahammad. / Anti-leukemic response of a NSAID, tolfenamic acid. In: Targeted Oncology. 2014 ; Vol. 9, No. 2. pp. 135-144.
@article{15898f238739498583840f4babc80407,
title = "Anti-leukemic response of a NSAID, tolfenamic acid",
abstract = "Tolfenamic acid (TA), a non-steroidal anti-inflammatory drug, is known to inhibit human cancer cells and mouse tumor growth in some cancer models; however, its anti-leukemic response has not been evaluated. TA targets specificity protein (Sp) transcription factors that mediate the expression of several genes associated with cancer including survivin, a key member of inhibitor of apoptosis protein family. Our aim was to test the anti-leukemic efficacy of TA in pre-clinical experiments. The anti-leukemic response of TA was determined using Jurkat and Nalm-6 cell lines. Cells were treated with increasing (25/50/75 μM) concentrations of TA, and cell viability was measured at 24, 48, and 72 h post-treatment. TA showed a steady and consistent decrease in cell viability following a clear dose and time dependent response. Apoptosis and cell cycle analysis was performed using flow cytometry. Results showed a significant increase in the apoptotic fraction (annexin V positive) following TA treatment, while cell cycle phase distribution analysis showed G0/G1 arrest. TA-induced apoptosis was further confirmed by examining the activation of caspase 3/7 and the expression of cleaved PARP. TA modulated the expression of critical candidates associated with the early phases of cell cycle and validated its efficacy in causing G0/G 1 arrest. The Western blot results revealed that TA significantly decreases Sp1 and survivin expression. These results demonstrate that the anti-leukemic response of TA occurs potentially through targeting Sp1 and inhibiting survivin and suggest the efficacy of TA as a novel therapeutic agent for leukemia.",
keywords = "Leukemia, NSAID, Sp1, Survivin, Tolfenamic acid, Transcription factors",
author = "Sutphin, {Robert M.} and Connelly, {Sarah F.} and Lee, {Chris M.} and Sankpal, {Umesh Tanaji} and Don Eslin and Moeez Khan and Hima Pius and Basha, {Riyaz Mahammad}",
year = "2014",
month = "1",
day = "1",
doi = "10.1007/s11523-013-0274-9",
language = "English",
volume = "9",
pages = "135--144",
journal = "Targeted Oncology",
issn = "1776-2596",
publisher = "Springer Paris",
number = "2",

}

Sutphin, RM, Connelly, SF, Lee, CM, Sankpal, UT, Eslin, D, Khan, M, Pius, H & Basha, RM 2014, 'Anti-leukemic response of a NSAID, tolfenamic acid', Targeted Oncology, vol. 9, no. 2, pp. 135-144. https://doi.org/10.1007/s11523-013-0274-9

Anti-leukemic response of a NSAID, tolfenamic acid. / Sutphin, Robert M.; Connelly, Sarah F.; Lee, Chris M.; Sankpal, Umesh Tanaji; Eslin, Don; Khan, Moeez; Pius, Hima; Basha, Riyaz Mahammad.

In: Targeted Oncology, Vol. 9, No. 2, 01.01.2014, p. 135-144.

Research output: Contribution to journalArticle

TY - JOUR

T1 - Anti-leukemic response of a NSAID, tolfenamic acid

AU - Sutphin, Robert M.

AU - Connelly, Sarah F.

AU - Lee, Chris M.

AU - Sankpal, Umesh Tanaji

AU - Eslin, Don

AU - Khan, Moeez

AU - Pius, Hima

AU - Basha, Riyaz Mahammad

PY - 2014/1/1

Y1 - 2014/1/1

N2 - Tolfenamic acid (TA), a non-steroidal anti-inflammatory drug, is known to inhibit human cancer cells and mouse tumor growth in some cancer models; however, its anti-leukemic response has not been evaluated. TA targets specificity protein (Sp) transcription factors that mediate the expression of several genes associated with cancer including survivin, a key member of inhibitor of apoptosis protein family. Our aim was to test the anti-leukemic efficacy of TA in pre-clinical experiments. The anti-leukemic response of TA was determined using Jurkat and Nalm-6 cell lines. Cells were treated with increasing (25/50/75 μM) concentrations of TA, and cell viability was measured at 24, 48, and 72 h post-treatment. TA showed a steady and consistent decrease in cell viability following a clear dose and time dependent response. Apoptosis and cell cycle analysis was performed using flow cytometry. Results showed a significant increase in the apoptotic fraction (annexin V positive) following TA treatment, while cell cycle phase distribution analysis showed G0/G1 arrest. TA-induced apoptosis was further confirmed by examining the activation of caspase 3/7 and the expression of cleaved PARP. TA modulated the expression of critical candidates associated with the early phases of cell cycle and validated its efficacy in causing G0/G 1 arrest. The Western blot results revealed that TA significantly decreases Sp1 and survivin expression. These results demonstrate that the anti-leukemic response of TA occurs potentially through targeting Sp1 and inhibiting survivin and suggest the efficacy of TA as a novel therapeutic agent for leukemia.

AB - Tolfenamic acid (TA), a non-steroidal anti-inflammatory drug, is known to inhibit human cancer cells and mouse tumor growth in some cancer models; however, its anti-leukemic response has not been evaluated. TA targets specificity protein (Sp) transcription factors that mediate the expression of several genes associated with cancer including survivin, a key member of inhibitor of apoptosis protein family. Our aim was to test the anti-leukemic efficacy of TA in pre-clinical experiments. The anti-leukemic response of TA was determined using Jurkat and Nalm-6 cell lines. Cells were treated with increasing (25/50/75 μM) concentrations of TA, and cell viability was measured at 24, 48, and 72 h post-treatment. TA showed a steady and consistent decrease in cell viability following a clear dose and time dependent response. Apoptosis and cell cycle analysis was performed using flow cytometry. Results showed a significant increase in the apoptotic fraction (annexin V positive) following TA treatment, while cell cycle phase distribution analysis showed G0/G1 arrest. TA-induced apoptosis was further confirmed by examining the activation of caspase 3/7 and the expression of cleaved PARP. TA modulated the expression of critical candidates associated with the early phases of cell cycle and validated its efficacy in causing G0/G 1 arrest. The Western blot results revealed that TA significantly decreases Sp1 and survivin expression. These results demonstrate that the anti-leukemic response of TA occurs potentially through targeting Sp1 and inhibiting survivin and suggest the efficacy of TA as a novel therapeutic agent for leukemia.

KW - Leukemia

KW - NSAID

KW - Sp1

KW - Survivin

KW - Tolfenamic acid

KW - Transcription factors

UR - http://www.scopus.com/inward/record.url?scp=84902535399&partnerID=8YFLogxK

U2 - 10.1007/s11523-013-0274-9

DO - 10.1007/s11523-013-0274-9

M3 - Article

C2 - 23609055

AN - SCOPUS:84902535399

VL - 9

SP - 135

EP - 144

JO - Targeted Oncology

JF - Targeted Oncology

SN - 1776-2596

IS - 2

ER -

Sutphin RM, Connelly SF, Lee CM, Sankpal UT, Eslin D, Khan M et al. Anti-leukemic response of a NSAID, tolfenamic acid. Targeted Oncology. 2014 Jan 1;9(2):135-144. https://doi.org/10.1007/s11523-013-0274-9