title: Apoptotic Effect of Tolfenamic Acid in KB Human Oral Cancer Cells: Possible Involvement of the p38 MAPK Pathway.
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.
authors.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.
authors.forename: Jun-Hee
authors.initials: JH
authors.lastname: Kim
authors.forename: Ji-Youn
authors.initials: JY
authors.lastname: Jung
authors.forename: Jung-Hyun
authors.initials: JH
authors.lastname: Shim
authors.forename: Jin
authors.initials: J
authors.lastname: Kim
authors.forename: Kyeong-Hee
authors.initials: KH
authors.lastname: Choi
authors.forename: Ji-Ae
authors.initials: JA
authors.lastname: Shin
authors.forename: Eun-Sun
authors.initials: ES
authors.lastname: Choi
authors.forename: Syng-Ook
authors.initials: SO
authors.lastname: Lee
authors.forename: Sudhakar
authors.initials: S
authors.lastname: Chintharlapalli
authors.forename: Ki Han
authors.initials: KH
authors.lastname: Kwon
authors.forename: Dae-Ho
authors.initials: DH
authors.lastname: Leem
authors.forename: Nam-Pyo
authors.initials: NP
authors.lastname: Cho
authors.forename: Sung-Dae
authors.initials: SD
authors.lastname: Cho