K-3 VİTAMİNİNİN SIÇAN GLİOMA (C6) ve İNSAN GLİOBLASTOMA MULTİFORME HÜCRE ÇOĞALMASINA İN VİTRO ETKİLERİ

Year 2005, Volume: 6 Issue: 1, 21 - 25, 01.04.2005

Pınar Öztopçu Selda Kabadere Ruhi Uyar

Abstract

Amaç:Glioblastoma multiforme beyin dokusu içerisine hızla yayılan ve onu yıkıma uğratan, sinir sistemindegörülme sıklığı yüksek oldukça tehlikeli bir tümör çeşididir. K-3 vitamininin çeşitli kanser hücre dizileri üzerindehücre çoğalmasını baskılayıcı etkisi olduğu bildirilmektedir. Çalışmamızda K-3 vitamininin, sıçan glioma (C6)ve insan glioblastoma multiforme hücrelerinin çoğalması üzerindeki baskılayıcı etkilerini karşılaştırarakbelirlemeyi amaçladık.Yöntem:K-3 vitamininin 1, 10, 25, 50, 75 ve 100 M dozlarının hücre çoğalması üzerindeki etkilerini, besiortamına ilave edildikten 24 saat sonra 3-(4,5-dimethylthiazol-2-yl)-2,5-diphenyltetrazolium bromide (MTT)yöntemi ile belirledik. Sonuçların istatistiksel değerlendirmesini tek yönlü varyans analizi ardından, Tukey'inçoklu karşılaştırma yöntemi ile yaptık.Bulgular:C6 ve insan glioblastoma multiforme hücre dizileri üzerinde K-3 vitamininin belirlenen dozlarınınhücre yaşam oranı üzerindeki etkilerini belirledik. Hücrelerin çoğalmasını % 50 oranında baskılayan doz olarakbilinen IC değerlerini C6 hücreleri için 41 M, glioblastoma multiforme hücreleri için 24 ve 23 M olarakbelirledik.Sonuçlar:Çalışmamızda, K-3 vitamininin hem C6 hem de insan glioblastoma hücreleri üzerinde düşük dozlardaantiproliferatif etkisi olduğu sonucuna vardık. Bulgularımızın, K-3 vitamini ve glioblastoma multiformeüzerinde yapılacak başka in vitro ve in vivo çalışmalara ışık tutacağına inanmaktayız

Keywords

Glioma, K-3 vitamini, hücre çoğalması, in vitro

Effects of Vitamin K-3 on Growth Inhibition of Rat glioma Cell (C6) and Human Glioblastoma Multiforme in Vitro

Abstract

Objectives: Glioblastoma multiforme is characterized as a highly invasive and rapidly growing astrocytoma. Previous studies have reported that vitamin K-3 inhibits cell growth of many types of malignant tumor cell lines. In this study we aimed to investigate the possible inhibitory effect of vitamin K-3 on rat glioma (C6) and human glioblastoma multiforme cells. Method:The cells were exposed to 1, 10, 25, 50, 75 and 100 M of vitamin K-3 for 24 hours. Cell viability was estimated by 3-(4,5-dimethylthiazol-2-yl)-2,5-diphenyltetrazolium bromide (MTT) assay. For statistical analysis one-way ANOVA test and then Tukey's multiple comparison test were used. Results: The IC50 values of vitamin K-3 were calculated as 41 M for C6, and 24 M and 23 M for human glioblastoma multiforme cells. Conclusion: We have found that at low concentrations vitamin K-3 has an antiproliferative effect on both C6 and human glioma cells. We believe that all these findings should contribute to other in vitro or in vivo studies on vitamin K-3 and glioblastoma multiforme cells.

Keywords

Glioma, vitamin K-3, cell proliferation, in vitro

References

• 1. Louis DN, Cavenee WK. Neoplasms of the central nervous system. In: DeVita, V.T., Hellman, S., and Rosenberg, S.A, eds; Cancer: principle and practice of oncology, 5 th ed. Philadelphia: Lippincott-Raven Publishers, 1997; 2013-2017.
• 2. Yaltkaya K, Balkan S, Oguz Y. Nöroloji Ders Kitabı, PalmeYayıncılık,Ankara, 1998; 292.
• 3. Bunin GG, Kuijten RR, Boesel PC. Materyal diet and risk of astrocytic glioma in children :report from the Childrens Cancer Group (United States and Canada). Cancer Cause Control 1994; 5 (2):177-187.
• 4. Mikkelsen T. Cytostatic agents in the management of malignant gliomas. Cancer Control:JMCC 1998; 5(2):150-162.
• 5. Salford LG, Siesjö P, Skagerberg G, Persson BRR, Larsson EM, Lindvall M, Visse E, Widegren B. Search for effective therapy against glioblastoma multiformeclinical immunisation with autologous glioma cells transduced with the human interferon- gene. International Congress Series 2002; 1247:211-220.
• 6. Raju TN. The Nobel chronicles. Lancet 1999; 353:761.
• 7. Suttie JW. The importance of menaquinones in human nutrition.Annu Rev Nutr 1995; 15:399-417.
• 8. Prasad KN, Prasad JE, Sakamoto A. Vitamin K (menadione) inhibits the growth of mammalian tumor cells in culture. Life Sci 1981; 13:1387-1392.
• 9. Ngo EO, Sun TP, Chang JY, Wang CC, Chi KW, Cheng AL, Nutter LM. Menadioneinduced DNA damage in a human tumor cell line. Biochem Pharmacol 1991; 42(10):1961-1968.
• 10. Nutter LM, Cheng AL, Hung HL, Hsieh RK, Ngo EO, Liu TW. Menadione: spectrum of anticancer activity and effects on nucleotide metabolism in human neoplastic cell lines. Biochem Pharm. 1991; 41:1283- 1292.
• 11. Durmaz R, Deliorman S, Işıksoy S, Uyar R, Erol K and Tel E: Antiproliferative properties of the Lazaroids U- 83836E and U-74389G on glioma cells in vitro. Pathol Oncol Res 1999; 5(3):223-228.
• 12. Unterman TG, Glick RP, Waites GT, Bell SC. Production of insulin-like growth factor-binding proteins by human central nervous system tumors. Cancer Res 1991; 51:3030-3036.
• 13. Thomas DGT, Darling JL, Paul EA, Mott TJ, Godlee JN, Tobias JS, Capra LG, Collins CD, Mooney C, Bozek T, Finn GP, Arigbabu SO, Bullard DE, Shannon N, Freshney RI. Assay of anti-cancer drugs in tissue culture: relationship of relapse free interval (RFI) and in vitro chemosensitivity in patients with malignant cerebral glioma. Br J Cancer 1985; 51:525-532.
• 14. Mosmann T. Rapid calorimetric assay for cellular growth and survival: Application to proliferation and cytotoxicity assay. J Immunol Methods 1983; 65:55- 63.
• 15. Alley MC, Scudiero DA, Monks A, Hursey ML, Czerwinski MJ, Fine DL, Abbott BJ, Mayo JG, Shoemaker RH, Boyd MR. Feasibility of drug screening with panels of human tumor cell lines using a microculture tetrazolium assay. Cancer Res 1988; 48:589-601.
• 16. Abe K, Matsuki N. Measurement of cellular 3-(4,5- dimethylthiazol-2-yl)-2,5-diphenytetrazolium bromide (MTT) reduction activity and lactate dehydrogenase release using MTT. Neurosci Res 2000; 38:325-329.
• 17. Wu FYH, Liao WC, Chang HM. Comparison of antitumor activity of vitamins K , K and K on human tumor cells by two (MTT and SRB) cell viability assays. Life Sci 1993; 52(22):1797-1804.
• 18. Nishikawa Y, Carr BI,Wang, M, Kar S, Finn F, Dowd P, Zheng Z, Kerns J. Growth inhibition of hepatoma cells induced by vitamin K and its analogs. J. Biol. Chem 1995; 270(47):28304-28310.
• 19. Sata N, Stumpe KH, Han B, Haussinger D, Niederau C. Menadione induces both necrosis and apoptosis in rat pancreatic acinar AR4-2J cells. Free Rad Biol Med 1997; 23(6):844-850.
• 20. Buckman TD, Sutphin MS, Mitrovic B. Oxidative stress in a clonal cell line of neuronal origin: effects of antioxidant enzyme modulation. J Neurochem 1993; 60(6):2046-2058.
• 21. Servitja JM, Masgrau R, Pardo R, Sarri E, Picatoste F. Effects of oxidative stress on phospho lipid signaling in rat cultured astrosit and brain slices. J Neurochem 2000; 75:788-794.
• 22. Desagher S, Glowinski J, Premont J. Astrocytes protect neurons from hydrogen peroxide toxicity. J Neurosci 1996; 16(8):2553-2562.
• 23. Sun LK, Yoshii Y, Miyagi K. Cytotoxic effect through Fas/APO-1 expression due to vitamin K in human glioma cells. J Neurooncol 2000; 47:31-38.
• 24. Wang Z, Wang M, Finn F, Carr BI. The growth inhibitory effects of vitamin K and their actions on gene expression. Hepatology 1995; 22(3):876-882.
• 25. Lamson DW, Plaza SM. The anticancer effects of vitamin K.Altern Med Rev 2003, 8(3):303-318.
• 26. Lagrange P, Romero IA, Minn A, Revest PA. Transendothelial permeability changes induced by free radicals in an in vitro model of the blood-brain barrier. Free Rad Biol Med 1999; 27:667-672.