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Apoptotic Effect of Tolfenamic Acid in KB Human Oral Cancer Cells: Possible Involvement of the p38 MAPK Pathway.

Kim JH, Jung JY, Shim JH, Kim J, Choi KH, Shin JA, Choi ES, Lee SO, Chintharlapalli S, Kwon KH, Leem DH, Cho NP, Cho SD - J Clin Biochem Nutr (2010)

Bottom Line: The results showed that tolfenamic acid does not alter the expression of the COX proteins, but it inhibits cell growth and induces apoptosis as evidenced by the annexin V positivity, sub-G(1) population, nuclear fragmentation and the cleavage of poly ADP-ribose polymerase.In addition, tolfenamic acid also leads to a loss of the mitochondrial membrane potential in KB cells.These effects are related to the activation of p38 mitogen-activated protein kinase (MAPK) pathway.

View Article: PubMed Central - PubMed

Affiliation: Department of Oral Pathology, School of Dentistry and Institute of Oral Bioscience, Brain Korea 21 project, Chonbuk National University, Jeonju 561-756, Republic of Korea.

ABSTRACT
Nonsteroidal anti-inflammatory drugs (NSAIDs) are known to inhibit cancer growth by inhibiting the activity of cyclooxygenase (COX). However, there is increasing evidence that the COX-independent pathway may be also involved in the inhibitory effect of NSAIDs against tumor progression. Tolfenamic acid is a NSAID that exhibits anticancer activity in pancreatic and colorectal cancer models. In the present study, the anti-tumor effect of tolfenamic acid in KB human oral cancer cells is investigated. The results showed that tolfenamic acid does not alter the expression of the COX proteins, but it inhibits cell growth and induces apoptosis as evidenced by the annexin V positivity, sub-G(1) population, nuclear fragmentation and the cleavage of poly ADP-ribose polymerase. In addition, tolfenamic acid also leads to a loss of the mitochondrial membrane potential in KB cells. These effects are related to the activation of p38 mitogen-activated protein kinase (MAPK) pathway. These results suggest that tolfenamic acid-induced apoptotic cell death inhibits cancer growth by activating the p38 MAPK pathway for cancer prevention.

No MeSH data available.


Related in: MedlinePlus

A, The structure of tolfenamic acid; B, The effect of 50, 75 and 100 µM of tolfenamic acid (one of nonsteroidal anti-inflammatory drugs (NSAIDs) for 48 h on the expressions of cyclooxygenase (COX) proteins in KB cells. Immunoblot detection of the COX-1 and COX-2 proteins in whole cell lysates. C, Immunoblot detection of COX-2 protein in whole cell lysates treated with dimethyl sulfoxide (DMSO), 100 µM of tolfenamic acid, and 60 µM of Celecoxib. Actin was used to normalize the protein loading from each treatment.
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Related In: Results  -  Collection


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Figure 1: A, The structure of tolfenamic acid; B, The effect of 50, 75 and 100 µM of tolfenamic acid (one of nonsteroidal anti-inflammatory drugs (NSAIDs) for 48 h on the expressions of cyclooxygenase (COX) proteins in KB cells. Immunoblot detection of the COX-1 and COX-2 proteins in whole cell lysates. C, Immunoblot detection of COX-2 protein in whole cell lysates treated with dimethyl sulfoxide (DMSO), 100 µM of tolfenamic acid, and 60 µM of Celecoxib. Actin was used to normalize the protein loading from each treatment.

Mentions: The poly ADP-ribose polymerase (PARP) antibody was obtained from BD PharmingenTM (San Jose, CA). The antibody for COX-1 and actin was purchased from Santa Cruz Biotechnology (Santa Cruz, CA). The COX-2 antibody was purchased from Cayman (Ann Arbor, MI). The antibodies for phosphor-p38 and total p38 were supplied by Cell Signaling Technology (Beverly, MA). SB203580 and Propidium Iodide were obtained Calbiochem (San Diego, CA) and RNase A was obtained from Sigma-Aldrich Korea (Yongin city, Korea). Tolfenamic acid (Fig. 1A) was purchased from Dae He Chemical Co. (Shihung, Korea).


Apoptotic Effect of Tolfenamic Acid in KB Human Oral Cancer Cells: Possible Involvement of the p38 MAPK Pathway.

Kim JH, Jung JY, Shim JH, Kim J, Choi KH, Shin JA, Choi ES, Lee SO, Chintharlapalli S, Kwon KH, Leem DH, Cho NP, Cho SD - J Clin Biochem Nutr (2010)

A, The structure of tolfenamic acid; B, The effect of 50, 75 and 100 µM of tolfenamic acid (one of nonsteroidal anti-inflammatory drugs (NSAIDs) for 48 h on the expressions of cyclooxygenase (COX) proteins in KB cells. Immunoblot detection of the COX-1 and COX-2 proteins in whole cell lysates. C, Immunoblot detection of COX-2 protein in whole cell lysates treated with dimethyl sulfoxide (DMSO), 100 µM of tolfenamic acid, and 60 µM of Celecoxib. Actin was used to normalize the protein loading from each treatment.
© Copyright Policy - open-access
Related In: Results  -  Collection

Show All Figures
getmorefigures.php?uid=PMC2901767&req=5

Figure 1: A, The structure of tolfenamic acid; B, The effect of 50, 75 and 100 µM of tolfenamic acid (one of nonsteroidal anti-inflammatory drugs (NSAIDs) for 48 h on the expressions of cyclooxygenase (COX) proteins in KB cells. Immunoblot detection of the COX-1 and COX-2 proteins in whole cell lysates. C, Immunoblot detection of COX-2 protein in whole cell lysates treated with dimethyl sulfoxide (DMSO), 100 µM of tolfenamic acid, and 60 µM of Celecoxib. Actin was used to normalize the protein loading from each treatment.
Mentions: The poly ADP-ribose polymerase (PARP) antibody was obtained from BD PharmingenTM (San Jose, CA). The antibody for COX-1 and actin was purchased from Santa Cruz Biotechnology (Santa Cruz, CA). The COX-2 antibody was purchased from Cayman (Ann Arbor, MI). The antibodies for phosphor-p38 and total p38 were supplied by Cell Signaling Technology (Beverly, MA). SB203580 and Propidium Iodide were obtained Calbiochem (San Diego, CA) and RNase A was obtained from Sigma-Aldrich Korea (Yongin city, Korea). Tolfenamic acid (Fig. 1A) was purchased from Dae He Chemical Co. (Shihung, Korea).

Bottom Line: The results showed that tolfenamic acid does not alter the expression of the COX proteins, but it inhibits cell growth and induces apoptosis as evidenced by the annexin V positivity, sub-G(1) population, nuclear fragmentation and the cleavage of poly ADP-ribose polymerase.In addition, tolfenamic acid also leads to a loss of the mitochondrial membrane potential in KB cells.These effects are related to the activation of p38 mitogen-activated protein kinase (MAPK) pathway.

View Article: PubMed Central - PubMed

Affiliation: Department of Oral Pathology, School of Dentistry and Institute of Oral Bioscience, Brain Korea 21 project, Chonbuk National University, Jeonju 561-756, Republic of Korea.

ABSTRACT
Nonsteroidal anti-inflammatory drugs (NSAIDs) are known to inhibit cancer growth by inhibiting the activity of cyclooxygenase (COX). However, there is increasing evidence that the COX-independent pathway may be also involved in the inhibitory effect of NSAIDs against tumor progression. Tolfenamic acid is a NSAID that exhibits anticancer activity in pancreatic and colorectal cancer models. In the present study, the anti-tumor effect of tolfenamic acid in KB human oral cancer cells is investigated. The results showed that tolfenamic acid does not alter the expression of the COX proteins, but it inhibits cell growth and induces apoptosis as evidenced by the annexin V positivity, sub-G(1) population, nuclear fragmentation and the cleavage of poly ADP-ribose polymerase. In addition, tolfenamic acid also leads to a loss of the mitochondrial membrane potential in KB cells. These effects are related to the activation of p38 mitogen-activated protein kinase (MAPK) pathway. These results suggest that tolfenamic acid-induced apoptotic cell death inhibits cancer growth by activating the p38 MAPK pathway for cancer prevention.

No MeSH data available.


Related in: MedlinePlus