Effect of α-tocopheryl succinate on the molecular damage induced by indomethacin in C6 glioma cells

Pekmez,Murat; Önay-Uçar,Evren; Arda,Nazlı

doi:10.3892/etm.2014.2101

Effect of α-tocopheryl succinate on the molecular damage induced by indomethacin in C6 glioma cells

Authors:
- Murat Pekmez
- Evren Önay-Uçar
- Nazlı Arda
View Affiliations

Affiliations: Department of Molecular Biology and Genetics, Faculty of Science, Istanbul University, Istanbul 34134, Turkey
Published online on: December 3, 2014 https://doi.org/10.3892/etm.2014.2101
Pages: 585-590

Metrics: Total Views: 0 (Spandidos Publications: | PMC Statistics: )

Metrics: Total PDF Downloads: 0 (Spandidos Publications: | PMC Statistics: )

Cited By (CrossRef): 0 citations Loading Articles...

Abstract

Indomethacin is a member of the non-steroidal anti‑inflammatory drug (NSAID) class, which has great potential for use in the treatment of glioma. However, it induces the generation of reactive oxygen species (ROS) and causes molecular damage while inducing its effects. Vitamin E is widely used in the complementary therapy of cancers. The main goal of the present study was to investigate the effects of α-tocopheryl succinate (α-TOS) against the oxidative damage induced by indomethacin in C6 glioma cells. Cells were treated with 10 µM α-TOS alone or in combination with 200 µM indomethacin for two days. The intracellular ROS level, molecular damage as revealed by lipid peroxidation and protein carbonyl formation, and the COX activity in C6 glioma cells were measured. Treatment of the cells with α-TOS and indomethacin, alone or in combination, caused the levels of ROS generation and protein damage to increase, but protected against lipid peroxidation and reduced COX activity.

View Figures

View References

1	Block IK, Koch CA, Mead NM, et al: Impact of antioxidant supplementation on chemotherapeutic efficacy: A systematic review of the evidence from randomized controlled trials. Cancer Treat Rev. 33:407–418. 2007. View Article : Google Scholar : PubMed/NCBI
2	Drisko AJ, Chapman J and Hunter JV: The use of antioxidant therapies during chemotherapy. Gynecol Oncol. 88:434–439. 2003. View Article : Google Scholar : PubMed/NCBI
3	Teicher BA, Schwartz JL, Holden SA, Ara G and Northey D: In vivo modulation of several anticancer agents by β-carotene. Cancer Chemoth Pharmacol. 34:235–241. 1994. View Article : Google Scholar
4	Mackerras D, Irwig L, Simpson JM, et al: Randomized double-blind trial of beta-carotene and vitamin C in women with minor cervical abnormalities. Brit J Cancer. 79:1448–1453. 1999. View Article : Google Scholar : PubMed/NCBI
5	Lamson DW and Brignall MS: Antioxidants and cancer therapy II: quick reference guide. Altern Med Rev. 5:152–163. 2000.PubMed/NCBI
6	Rama B and Prasad KN: Study on the specificity of α-tocopheryl (vitamin E) acid succinate effects on the melanoma, glioma and neuroblastoma cells in culture. Proc Soc Exp Biol Med. 174:302–307. 1983. View Article : Google Scholar : PubMed/NCBI
7	Azzi A, Gysin R, Kempná P, et al: The role of α-tocopherol in preventing disease: from epidemiology to molecular events. Mol Aspects Med. 24:325–336. 2003. View Article : Google Scholar : PubMed/NCBI
8	Shiff SJ, Koutsos MI, Qiao L and Rigas B: Nonsteroidal antiinflammatory drugs inhibit the proliferation of colon adenocarcinoma cells: effects on cell cycle and apoptosis. Exp Cell Res. 222:179–188. 1996. View Article : Google Scholar : PubMed/NCBI
9	Smith ML, Hawcroft G and Hull MA: The effect of non-steroidal anti-inflammatory drugs on human colorectal cancer cells: evidence of different mechanisms of action. Eur J Cancer. 36:664–674. 2000. View Article : Google Scholar : PubMed/NCBI
10	Cuzick J, Otto F, Baron JA, et al: Aspirin and non-steroidal anti-inflammatory drugs for cancer prevention: an international consensus statement. Lancet Oncol. 10:501–507. 2009. View Article : Google Scholar : PubMed/NCBI
11	Gupta RA, Tan J, Krause WF, et al: Prostacyclin-mediated activation of peroxisome peroxiome proliferator-activated receptor delta in colorectal cancer. Proc Natl Acad Sci USA. 97:13275–13280. 2000. View Article : Google Scholar
12	Yasumaru M, Tsuji S, Tsujii M, et al: Inhibition of angiotensin II activity enhanced the antitumor effect of cyclooxygenase-2 inhibitors via insulin-like growth factor I receptor pathway. Cancer Res. 63:6726–6734. 2003.PubMed/NCBI
13	Bernardi A, Jacques-Silva MC, Delgado-Cañedo A, Lenz G and Battastini AMO: Nonsteroidal anti-inflammatory drugs inhibit the growth of C6 and U138-MG glioma cell lines. Eur J Pharmacol. 532:214–222. 2006. View Article : Google Scholar : PubMed/NCBI
14	Amin R, Kamitani H, Sultana H, et al: Aspirin and indomethacin exhibit antiproliferative effects and induce apoptosis in T98G human glioblastoma cells. Neurol Res. 25:370–376. 2003. View Article : Google Scholar : PubMed/NCBI
15	Holt S and Fowler CJ: Anandamide metabolism by fatty acid amide hydrolase in intact C6 glioma cells. Increased sensitivity to inhibition by ibuprofen and flurbiprofen upon reduction of extra but not intracellular pH. Naunyn Schmiedebergs Arch Pharmacol. 367:237–244. 2003. View Article : Google Scholar : PubMed/NCBI
16	Ribeiro G, Benadiba M, Colquhoun A and Silva DO: Diruthenium (II, III) complexes of ibuprofen, aspirin, naproxen and indomethacin non-steroidal anti-inflammatory drugs: Synthesis, characterization and their effects on tumor-cell proliferation. Polyhedron. 27:1131–1137. 2008. View Article : Google Scholar
17	Lee BS, Nalla AK, Stock IR, et al: Oxidative stimuli-responsive nanodrug of camptothecin kills gliobalstoma cells. Bioorg Med Chem Lett. 20:5262–5268. 2010. View Article : Google Scholar : PubMed/NCBI
18	Shono T, Tofilon PJ, Bruner JM, Owolabi O and Lang FF: Cyclooxygenase-2 expression in human gliomas: prognostic significance and molecular correlations. Cancer Res. 61:4375–4381. 2001.PubMed/NCBI
19	Kürzel F, Hagel Ch, Zapf S, et al: Cyclo-oxygenase inhibitors and thromboxane synthase inhibitors differentially regulate migration arrest, growth inhibition and apoptosis in human glioma cells. Acta Neurochir (Wien). 144:71–87. 2002. View Article : Google Scholar
20	Nathoo N, Barnett GH and Golubic M: The eicosanoid cascade: possible role in gliomas and meningiomas. J Clin Pathol. 57:6–13. 2004. View Article : Google Scholar
21	New P: Cyclooxygenase in the treatment of glioma: its complex role in signal transduction. Cancer Control. 11:152–164. 2004.PubMed/NCBI
22	Wang M, Yoshida D, Liu S and Teramoto A: Inhibition of cell invasion by indomethacin on glioma cell lines: in vitro study. J Neurooncol. 72:1–9. 2005. View Article : Google Scholar : PubMed/NCBI
23	Grubbs CJ, Lubet RA, Koki AT, et al: Celecoxib inhibits N-butyl-N-(4-hydroxybutyl)-nitrosamine-induced urinary bladder cancers in male B6D2F1 mice and female Fischer-344 rats. Cancer Res. 60:5599–5602. 2000.PubMed/NCBI
24	Williams CS, Watson AJM, Sheng H, et al: Celecoxib prevents tumor growth in vivo without toxicity to normal gut: lack of correlation between in vitro and in vivo models. Cancer Res. 60:6045–6051. 2000.PubMed/NCBI
25	Baek JS, Wilson CL, Lee CH and Eling TE: Dual function of nonsteroidal anti-inflammatory drugs (NSAIDs): inhibition of cyclooxygenase and induction of NSAID-activated gene. J Pharmocol Exp Ther. 301:1126–1131. 2002. View Article : Google Scholar
26	Shiff SJ, Shivaprasad P and Santini DL: Cyclooxygenase inhibitors: drugs for cancer prevention. Curr Opin Pharmacol. 3:352–361. 2003. View Article : Google Scholar : PubMed/NCBI
27	Mosmann T: Rapid colorimetric assay for cellular growth and survival application to proliferation and cytotoxicity assay. J Immunol Methods. 65:551983. View Article : Google Scholar : PubMed/NCBI
28	Negre-Salvayre A, Augé N, Duval C, et al: Detection of intracellular reactive oxygen species in cultured cells using fluorescent probes. Method Enzymol. 352:62–71. 2002. View Article : Google Scholar
29	Draper HH and Hadley M: Malondialdehyde determination as an index of lipid peroxidation. Methods Enzymol. 186:421–431. 1990. View Article : Google Scholar
30	Stoscheck CM: Quantitation of protein. Methods Enzymol. 182:50–69. 1990. View Article : Google Scholar : PubMed/NCBI
31	Gravel P: Protein Blotting by the Semidry method. The Protein Protocols Handbook. 2nd edition. Smith Bryan John: Humana Press; Totowa, NJ: pp. 321–334. 2002, View Article : Google Scholar
32	Walker JM: Quantification of Proteins on Polyacrylamide Gels. The Protein Protocols Handbook. 2nd edition. Smith Bryan John: Humana Press; Totowa, NJ: pp. 237–243. 2002
33	Flower RJ, Cheung HS and Cushman DW: Quantitative determination of prostaglandins and malondialdehyde formed by the arachidonate oxygenase (prostaglandin synthetase) system of bovine seminal vesicle. Prostaglandins. 4:325–341. 1973. View Article : Google Scholar : PubMed/NCBI
34	Sivak-Sears NR, Schwartzbaum JA, Miike R, Moghadassi M and Wrensch M: Case-control study of use of nonsteroidal antiinflammatory drugs and glioblastoma multiforme. Am J Epidemiol. 159:1131–1139. 2004. View Article : Google Scholar : PubMed/NCBI
35	Courad JP, Besse D, Delchambre C, et al: Acetaminophen distribution in the rat central nervous system. Life Sci. 69:1455–1464. 2001. View Article : Google Scholar : PubMed/NCBI
36	Rao P and Knaus EE: Evolution of nonsteroidal anti-inflammatory drugs (NSAIDs): cyclooxygenase (COX) inhibition and beyond. J Pharm Pharm Sci. 11:81s–110s. 2008.
37	Conklin KA: Dietary antioxidants during cancer chemotherapy: impact on chemotherapeutic effectiveness and development of side effects. Nutr Cancer. 37:1–18. 2000. View Article : Google Scholar : PubMed/NCBI
38	Weijl NI, Cleton FJ and Osanto S: Free radicals and antioxidants in chemotherapy-induced toxicity. Cancer Treat Rev. 23:209–240. 1997. View Article : Google Scholar : PubMed/NCBI
39	Salganik IR, Albright DC, Rodgers J, et al: Dietary antioxidant depletion: enhancement of tumor apoptosis and inhibition of brain tumor growth in transgenic mice. Carcinogenesis. 21:909–914. 2000. View Article : Google Scholar : PubMed/NCBI
40	Ristimäki A, Sivula A, Lundin J, et al: Prognostic significance of elevated cyclooxygenase-2 expression in breast cancer. Cancer Res. 62:632–635. 2002.PubMed/NCBI
41	Ishibashi M, Bottone FG Jr, Taniura S, et al: The cyclooxygenase inhibitor indomethacin modulates gene expression and represses the extracellular matrix protein laminin gamma1 in human glioblastoma cells. Exp Cell Res. 302:244–252. 2005. View Article : Google Scholar
42	Constantinou C, Papas A and Constantinou AI: Vitamin E and cancer: An insight into the anticancer activities of vitamin E isomers and analogs. Int J Cancer. 123:739–752. 2008. View Article : Google Scholar : PubMed/NCBI
43	Ottino P and Duncan JR: Effect of vitamin E succinate on free radical formation, lipid peroxidation levels and cyclooxygenase activity in murine melanoma cells. Nutr Res. 17:661–676. 1997. View Article : Google Scholar
44	Stapelberg M, Gellert N, Swettenham E, et al: Alpha-tocopheryl succinate inhibits malignant mesothelioma by disrupting the fibroblast growth factor autocrine loop: mechanism and the role of oxidative stress. J Biol Chem. 280:25369–25376. 2005. View Article : Google Scholar : PubMed/NCBI
45	Naito Y and Yoshikawa T: Oxidative stress involvement and gene expression in indomethacin-induced gastropathy. Redox Rep. 11:243–253. 2006. View Article : Google Scholar
46	Maity P, Bindu S, Dey S, et al: Indomethacin, a non-steroidal anti-inflammatory grug, develops gastropathy by inducing reactive oxygen species-mediated mitochondrial pathology and associated apoptosis in gastric mucosa. J Biol Chem. 284:3058–3068. 2009. View Article : Google Scholar
47	O’Callaghan JP: Neurotypic and gliotypic proteins as biochemical markers of neurotoxicity. Neurotoxicol Teratol. 10:445–452. 1988. View Article : Google Scholar
48	Hrkal Z: On the way to functional genomics. Sb Lek. 104:217–222. 2003.PubMed/NCBI