Regulation of C6 glioma cell migration by thymol

Lee,Kang  Pa; Kim,Jai‑Eun; Park,Won‑Hwan; Hong,Heeok

doi:10.3892/ol.2016.4237

Regulation of C6 glioma cell migration by thymol

Authors:
- Kang Pa Lee
- Jai‑Eun Kim
- Won‑Hwan Park
- Heeok Hong
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Affiliations: Department of Physiology, School of Medicine, Konkuk University, Seoul 143‑701, Republic of Korea, Department of Pathology, College of Korean Medicine, Dongguk University, Goyang 410‑820, Republic of Korea, Department of Diagnostics, College of Korean Medicine, Dongguk University, Goyang 410‑820, Republic of Korea, Department of Medical Science, School of Medicine, Konkuk University, Seoul 143‑701, Republic of Korea
Published online on: February 17, 2016 https://doi.org/10.3892/ol.2016.4237
Pages: 2619-2624

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Abstract

Tumor cell motility exhibits a crucial role in tumor development. Therefore, the present study aimed to investigate whether thymol could reduce C6 glioma cell migration. Cell viability was determined using the EZ-Cytox Cell Viability kit. The scratch wound healing and Boyden chamber assays were performed to test C6 glioma cell migration in the presence of fetal bovine serum (FBS). Additionally, the study investigated whether signaling proteins relevant to C6 glioma cell migration, i.e., extracellular signal-regulated kinases (ERK)1/2, protein kinase Cα (PKCα), matrix metallopeptidase (MMP)9 and MMP2, were affected by thymol treatment. Up to 30 µM, thymol did not alter cell viability, whereas 100 µM thymol induced the death of ~20% of the cells. Furthermore, thymol (30 µM) significantly reduced FBS-induced migration. In the FBS-stimulated C6 glioma cells, thymol (30 µM) suppressed PKCα and ERK1/2 phosphorylation. MMP9 and MMP2 production was also significantly reduced by treatment with 30 µM thymol in the C6 glioma cells. Taken together, these results indicate that thymol attenuates C6 glioma cell migration. Additionally, the study suggests that the effect of thymol on the FBS-induced migration of C6 glioma cells affects PKCα and ERK1/2 signaling, and suppresses MMP9 and MMP2 production.

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1	Ostrom QT, Gittleman H, Fulop J, Liu M, Blanda R, Kromer C, Wolinsky Y, Kruchko C and Barnholtz-Sloan JS: CBTRUS statistical report: Primary brain and central nervous system tumors diagnosed in the United States in 2008–2012. Neuro Oncol. 17(Suppl 4): iv1–iv622015. View Article : Google Scholar
2	Ostrom QT, Bauchet L, Davis FG, Deltour I, Fisher JL, Langer CE, Pekmezci M, Schwartzbaum JA, Turner MC, Walsh KM, et al: The epidemiology of glioma in adults: A “state of the science” review. Neuro Oncol. 16:896–913. 2014. View Article : Google Scholar : PubMed/NCBI
3	Belda-Iniesta C, de Castro Carpeño J, Casado Sáenz E, Cejas Guerrero P, Perona R and González Barón M: Molecular biology of malignant gliomas. Clin Transl Oncol. 8:635–641. 2006. View Article : Google Scholar : PubMed/NCBI
4	Coniglio SJ and Segall JE: Review: Molecular mechanism of microglia stimulated glioblastoma invasion. Matrix Biol. 32:372–380. 2013. View Article : Google Scholar : PubMed/NCBI
5	Qi ST, Liu Y, Pan J, Chotai S and Fang LX: A radiopathological classification of dural tail sign of meningiomas. J Neurosurg. 117:645–653. 2012. View Article : Google Scholar : PubMed/NCBI
6	Hess KR, Broglio KR and Bondy ML: Adult glioma incidence trends in the United States, 1977–2000. Cancer. 101:2293–2299. 2004. View Article : Google Scholar : PubMed/NCBI
7	Chinot OL, Macdonald DR, Abrey LE, Zahlmann G, Kerloëguen Y and Cloughesy TF: Response assessment criteria for glioblastoma: Practical adaptation and implementation in clinical trials of antiangiogenic therapy. Curr Neurol Neurosci Rep. 13:3472013. View Article : Google Scholar : PubMed/NCBI
8	Le DM, Besson A, Fogg DK, Choi KS, Waisman DM, Goodyer CG, Rewcastle B and Yong VW: Exploitation of astrocytes by glioma cells to facilitate invasiveness: A mechanism involving matrix metalloproteinase-2 and the urokinase-type plasminogen activator-plasmin cascade. J Neurosci. 23:4034–4043. 2003.PubMed/NCBI
9	Uhm JH, Dooley NP, Villemure JG and Yong VW: Glioma invasion in vitro: Regulation by matrix metalloprotease-2 and protein kinase C. Clin Exp Metastasis. 14:421–433. 1996. View Article : Google Scholar : PubMed/NCBI
10	Glassmann A, Reichmann K, Scheffler B, Glas M, Veit N and Probstmeier R: Pharmacological targeting of the constitutively activated MEK/MAPK-dependent signaling pathway in glioma cells inhibits cell proliferation and migration. Int J Oncol. 39:1567–1575. 2011.PubMed/NCBI
11	Soletti RC, Alves T, Vernal J, Terenzi H, Anderluh G, Borges HL, Gabilan NH and Moura-Neto V: Inhibition of MAPK/ERK, PKC and CaMKII signaling blocks cytolysin-induced human glioma cell death. Anticancer Res. 30:1209–1215. 2010.PubMed/NCBI
12	Strnisková M, Barancík M and Ravingerová T: Mitogen-activated protein kinases and their role in regulation of cellular processes. Gen Physiol Biophys. 21:231–255. 2002.PubMed/NCBI
13	Chen CM, Hsieh YH, Hwang JM, Jan HJ, Hsieh SC, Lin SH and Lai CY: Fisetin suppresses ADAM9 expression and inhibits invasion of glioma cancer cells through increased phosphorylation of ERK1/2. Tumour Biol. 36:3407–3415. 2015. View Article : Google Scholar : PubMed/NCBI
14	Mendes O, Kim HT, Lungu G and Stoica G: MMP2 role in breast cancer brain metastasis development and its regulation by TIMP2 and ERK1/2. Clin Exp Metastasis. 24:341–351. 2007. View Article : Google Scholar : PubMed/NCBI
15	Hu JG, Wang XF, Zhou JS, Wang FC, Li XW and Lü HZ: Activation of PKC-alpha is required for migration of C6 glioma cells. Acta Neurobiol Exp (Wars). 70:239–245. 2010.PubMed/NCBI
16	Köhrmann A, Kammerer U, Kapp M, Dietl J and Anacker J: Expression of matrix metalloproteinases (MMPs) in primary human breast cancer and breast cancer cell lines: New findings and review of the literature. BMC Cancer. 9:1882009. View Article : Google Scholar : PubMed/NCBI
17	Khasigov PZ, Podobed OV, Gracheva TS, Salbiev KD, Grachev SV and Berezov TT: Role of matrix metalloproteinases and their inhibitors in tumor invasion and metastasis. Biochemistry (Mosc). 68:711–717. 2003. View Article : Google Scholar : PubMed/NCBI
18	Undeğer U, Başaran A, Degen GH and Başaran N: Antioxidant activities of major thyme ingredients and lack of (oxidative) DNA damage in V79 Chinese hamster lung fibroblast cells at low levels of carvacrol and thymol. Food Chem Toxicol. 47:2037–2043. 2009. View Article : Google Scholar : PubMed/NCBI
19	Grommes C, Landreth GE, Sastre M, et al: Inhibition of in vivo glioma growth and invasion by peroxisome proliferator-activated receptor gamma agonist treatment. Mol Pharmacol. 70:1524–1533. 2006. View Article : Google Scholar : PubMed/NCBI
20	Deb DD, Parimala G, Saravana Devi S and Chakraborty T: Effect of thymol on peripheral blood mononuclear cell PBMC and acute promyelotic cancer cell line HL-60. Chem Biol Interact. 193:97–106. 2011. View Article : Google Scholar : PubMed/NCBI
21	Chang HT, Hsu SS, Chou CT, Cheng JS, Wang JL, Lin KL, Fang YC, Chen WC, Chien JM, Lu T, et al: Effect of thymol on Ca²⁺ homeostasis and viability in MG63 human osteosarcoma cells. Pharmacology. 88:201–212. 2011. View Article : Google Scholar : PubMed/NCBI
22	Hsu SS, Lin KL, Chou CT, Chiang AJ, Liang WZ, Chang HT, Tsai JY, Liao WC, Huang FD, Huang JK, et al: Effect of thymol on Ca2+ homeostasis and viability in human glioblastoma cells. Eur J Pharmacol. 670:85–91. 2011. View Article : Google Scholar : PubMed/NCBI
23	Kang SH, Kim YS, Kim EK, et al: Anticancer Effect of Thymol on AGS Human Gastric Carcinoma Cells. J Microbiol Biotechnol. 26:28–37. 2016.PubMed/NCBI
24	Archana PR, Rao Nageshwar B and Rao Satish BS: Modulation of gamma ray-induced genotoxic effect by thymol, a monoterpene phenol derivative of cymene. Integr Cancer Ther. 10:374–383. 2011. View Article : Google Scholar : PubMed/NCBI
25	Carduner L, Picot CR, Leroy-Dudal J, Blay L, Kellouche S and Carreiras F: Cell cycle arrest or survival signaling through αv integrins, activation of PKC and ERK1/2 lead to anoikis resistance of ovarian cancer spheroids. Exp Cell Res. 320:329–342. 2014. View Article : Google Scholar : PubMed/NCBI
26	Kim H, Zamel R, Bai XH and Liu M: PKC activation induces inflammatory response and cell death in human bronchial epithelial cells. PLoS One. 8:e641822013. View Article : Google Scholar : PubMed/NCBI
27	Hartleben B, Widmeier E, Suhm M, Worthmann K, Schell C, Helmstädter M, Wiech T, Walz G, Leitges M, Schiffer M and Huber TB: APKCλ/ι and aPKCζ contribute to podocyte differentiation and glomerular maturation. J Am Soc Nephrol. 24:253–267. 2013. View Article : Google Scholar : PubMed/NCBI
28	Tam WL, Lu H, Buikhuisen J, Soh BS, Lim E, Reinhardt F, Wu ZJ, Krall JA, Bierie B, Guo W, et al: Protein Kinase C α is a central signaling node and therapeutic target for breast cancer stem cells. Cancer Cell. 24:347–364. 2013. View Article : Google Scholar : PubMed/NCBI
29	Li Q, Fu GB, Zheng JT, He J, Niu XB, Chen QD, Yin Y, Qian X, Xu Q, Wang M, et al: NADPH oxidase subunit p22 (phox)-mediated reactive oxygen species contribute to angiogenesis and tumor growth through AKT and ERK1/2 signaling pathways in prostate cancer. Biochim Biophys Acta. 1833:3375–3385. 2013. View Article : Google Scholar : PubMed/NCBI
30	Sun J, Liu SZ, Lin Y, Cao XP and Liu JM: TGF-β promotes glioma cell growth via activating Nodal expression through Smad and ERK1/2 pathways. Biochem Biophys Res Commun. 443:1066–1072. 2014. View Article : Google Scholar : PubMed/NCBI