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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

Tolfenamic acid activates the mitochondrial apoptotic pathway. A, 3,3'-tetraethylbenzimidazolylcarbocyanine iodide (JC-1) assay. After applying 50, 75 and 100 µM of tolfenamic acid for 48 h, the JC-1 fluorescence shifted from red-orange to green, indicating depolarization of the mitochondrial membrane potential. B, the points are the mean ± SD of three independent experiments. *p<0.05 compared to the control group.
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Figure 4: Tolfenamic acid activates the mitochondrial apoptotic pathway. A, 3,3'-tetraethylbenzimidazolylcarbocyanine iodide (JC-1) assay. After applying 50, 75 and 100 µM of tolfenamic acid for 48 h, the JC-1 fluorescence shifted from red-orange to green, indicating depolarization of the mitochondrial membrane potential. B, the points are the mean ± SD of three independent experiments. *p<0.05 compared to the control group.

Mentions: The mitochondrial apoptotic events involved in tolfenamic acid-mediated apoptosis were assessed by examining the depolarization of the mitochondrial membrane potentials (MMPs) (Fig. 4). The results showed that tolfenamic acid depolarized the KB cell MMP 48 h after treatment in a concentration-dependent manner.


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)

Tolfenamic acid activates the mitochondrial apoptotic pathway. A, 3,3'-tetraethylbenzimidazolylcarbocyanine iodide (JC-1) assay. After applying 50, 75 and 100 µM of tolfenamic acid for 48 h, the JC-1 fluorescence shifted from red-orange to green, indicating depolarization of the mitochondrial membrane potential. B, the points are the mean ± SD of three independent experiments. *p<0.05 compared to the control group.
© Copyright Policy - open-access
Related In: Results  -  Collection

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

Figure 4: Tolfenamic acid activates the mitochondrial apoptotic pathway. A, 3,3'-tetraethylbenzimidazolylcarbocyanine iodide (JC-1) assay. After applying 50, 75 and 100 µM of tolfenamic acid for 48 h, the JC-1 fluorescence shifted from red-orange to green, indicating depolarization of the mitochondrial membrane potential. B, the points are the mean ± SD of three independent experiments. *p<0.05 compared to the control group.
Mentions: The mitochondrial apoptotic events involved in tolfenamic acid-mediated apoptosis were assessed by examining the depolarization of the mitochondrial membrane potentials (MMPs) (Fig. 4). The results showed that tolfenamic acid depolarized the KB cell MMP 48 h after treatment in a concentration-dependent manner.

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