Display options
Share it on

J Clin Biochem Nutr. 2010 Jul;47(1):74-80. doi: 10.3164/jcbn.10-02. Epub 2010 Jun 17.

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

Journal of clinical biochemistry and nutrition

Jun-Hee Kim, Ji-Youn Jung, Jung-Hyun Shim, Jin Kim, Kyeong-Hee Choi, Ji-Ae Shin, Eun-Sun Choi, Syng-Ook Lee, Sudhakar Chintharlapalli, Ki Han Kwon, Dae-Ho Leem, Nam-Pyo Cho, Sung-Dae Cho

Affiliations

  1. 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.

PMID: 20664734 PMCID: PMC2901767 DOI: 10.3164/jcbn.10-02

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.

Keywords: KB human oral cancer cells; apoptosis; mitochondrial membrane potential; p38 MAPK; tolfenamic acid

References

  1. Science. 1997 Jan 3;275(5296):90-4 - PubMed
  2. J Natl Cancer Inst. 2006 Jun 21;98(12):855-68 - PubMed
  3. J Biol Chem. 2001 May 25;276(21):18563-9 - PubMed
  4. Clin Cancer Res. 2001 Apr;7(4):861-7 - PubMed
  5. Br J Rheumatol. 1984 Feb;23(1):61-5 - PubMed
  6. Hepatogastroenterology. 1999 Jan-Feb;46(25):407-12 - PubMed
  7. Apoptosis. 2008 Dec;13(12):1450-64 - PubMed
  8. Cancer. 2002 Aug 15;95(4):801-7 - PubMed
  9. Science. 1997 Feb 21;275(5303):1129-32 - PubMed
  10. Am J Clin Pathol. 2002 Aug;118(2):194-201 - PubMed
  11. Cancer Res. 2007 Apr 1;67(7):3286-94 - PubMed
  12. Cancer Res. 1999 Mar 1;59(5):991-4 - PubMed
  13. Cell Immunol. 2002 Dec;220(2):96-106 - PubMed
  14. Cancer Res. 2000 Jul 15;60(14):3696-700 - PubMed
  15. Carcinogenesis. 2009 Jul;30(7):1193-201 - PubMed
  16. FASEB J. 2004 Dec;18(15):1946-8 - PubMed
  17. JAMA. 1999 Nov 24;282(20):1921-8 - PubMed
  18. Clin Cancer Res. 2000 Jun;6(6):2424-30 - PubMed
  19. Eur J Clin Pharmacol. 1978 Jul 30;13(5):331-44 - PubMed
  20. Int J Clin Pract. 2008 Mar;62(3):444-9 - PubMed
  21. Cancer Res. 2001 Jun 1;61(11):4375-81 - PubMed
  22. Mol Cancer Ther. 2008 Dec;7(12):3739-50 - PubMed
  23. Science. 2000 Nov 3;290(5493):989-92 - PubMed
  24. Cell. 1999 Oct 29;99(3):335-45 - PubMed
  25. J Biol Chem. 2003 Dec 12;278(50):50624-34 - PubMed
  26. Pharmacol Toxicol. 1994;75 Suppl 2:81-2 - PubMed
  27. Pharmacol Toxicol. 1994;75 Suppl 2:44-8 - PubMed

Publication Types