C6 sıçan glioma hücreleri üzerine aloe emodin ve cisplatinin etkilerinin iki ve üç boyutlu hücre kültür modellerinde incelenmesi

Amaç: Bu çalışmanın amacı, doğal bir antrakinon türevi olan aloe emodin ve organoplatinler grubundan kemoteropatik bir ilaç olan cisplatinin ayrı ayrı ve birarada kullanıldıklarında C6 glioma hücre soyu üzerine etkilerini iki ve üç boyutlu tümör hücre kültür modelleri kullanılarak incelemekti. Gereç ve yöntem: İki boyutlu kültürlerde iki ilacın ayrı ayrı ve birlikte kullanımları 12, 24, 48, 72. saatlerde hem hücre çoğalması, hem de hücre siklusu sentez fazı açısından incelendi. Üç boyutlu hücre kültürü modelinde ise her iki ilacın ayrı ayrı ve kombine kullanımları 72. saatte hücre siklusu sentez fazı ve hücre ince yapısı açısından değerlendirildi.Bulgular: Aloe emodin, iki boyutlu kültürde hücre çoğalmasını azaltıcı etki gösterdi ve hücre siklusu sentez fazı işaretlenmesinde azalma meydana getirdi (p

The effects of aloe emodin and cisplatin on rat glioma cell line in two and three-dimensional cell culture models

Objective: The aim of this study was to examine the effects of aloe emodin, a natural anthraqinone derivate, and cisplatin, a chemotherapeutic drug from organoplatins group, on C6 glioma cell line with the use of two and threedimensional tumour cell culture models. Materials and methods: For this purpose, the drugs were administered both alone and in combination for 12, 24, 48, 72 hours and the effects on cell proliferation and the S-phase fraction were determined in two-dimensional cell culture. In three-dimensional cell culture, the effects of two drugs used alone and in combination were studied at 72 h by determining the S-phase fraction and evaluating the ultrastructure of the cells.Results: Aloe emodin has reduced cell proliferation and S-phase fraction in two-dimensional cell culture (p

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1) Algier LA., Hanoğlu Z, Özden G, Kara F. The use of complementary and alternative (non-conventional) medicine in cancer patient in Turkey. Eur J Oncol Nurs 2005;9: 138-146.
2) Bell HS, Whittle IR, Walker M, Leaver HA, Wharton SB. The development of necrosis and apoptosis in glioma: experimental findings using spheroid culture systems. Neuropathol Appl Neurobiol 2001; 27:291-304.
3) Fenig E, Nordenberg J, Beery E, Sulkes J, Wasserman L. Combined effect of aloe-emodin and chemotheraeputic agents on the proliferation of an adherent variant cell line of Merkel cell carcinoma. Oncol Rep 2004;11:213-217.
4) Graham AC, Cloughesy TF. Brain tumor treatment: chemotherapy and other new developments. Semin Oncol Nurs 2004; 20:260-272.
5) Grobben B, De Deyn, PP, Slegers H. Rat C6 glioma as experimental model system for the study of glioblastoma growth and invasion. Cell Tissue Res 2002;310:257-270.
6) Hall MD, Martin C, Ferguson DJP, Phillips RM, Hambley TW, Callaghan R. Comperative efficacy of novel platinum (IV) compounds with established chemotherpeutic drugs in solid tumour models. Biochem Pharmaco 2004; 67:17-30.
7) Krajcı D, Mares V, Lisa V, Bottone MG. Pelliciari C. Intranuclear microtubules are hallmarks of an usual form of cell death in cisplatin-treated C6 glioma cells. Histochem. Cell Biol 2005;125:183-191.
8) Kunz-Schughart LA, Freyer JP, Hofstaedter F, Ebner R. The use of 3-D cultures for high-throughput screening: the multicellular spheroid model. J Biomol Screen 2004; 9: 273-285.
9) Kuo PL, Lin TC, Lin CC. The antiproliferative activity of aloeemodin is through p53-dependent and p21-dependent apoptotic pathway in human hepatoma cell lines. Life Sci 2002; 71:1879- 1892.
10) Maity TK, Mandal SC, Bhakta T, Pal M, Saha BP. Metabolism of 1,8-Dihidroxy 3-Hydroxy Methyl Anthraquinone (Aloe-emodin) isolated from the leaves of Cassia tora in albino rats. Phytother Res 2001;15:459-460.
11) Mijatovic S, Maksimovic-Ivanic D, Radovic J, Miljkovic Dj, Harhaji L, Vuckovic O, Stosic-Grujicic S. Stojkovic MM, Trajkovic V. Antiglioma action of aloe emodin: The role of ERK inhibition. Cell Mol. Life Sci 2005; 62: 589-598.
12) Mijatovic S, Maksimovic-Ivanic D, Radovic J, Miljkovic D, Kaludjerovic Sabo, TJ, Trajkovic V. Aloe emodin decreases the ERK- dependent anticancer activity of cisplatin, Cell Mol Life Sci 2005; 62:1275-1282.
13) Molassiotis A, Fernandez-Ortega P, Pud D, Ozden G. Use of complementary and alternative medicine in cancer patients: A European survey. Annals of Oncology 2005; 16: 655-663.
14) Niggeman B, Grüber C. Side effects of complementary and alternative medicine. Allergy 2003;58:707-716.
15) Noda S, Yoshimura S, Sawada M, Naganawa T, Iwama T, Nakashima, S, Sakai N. Role of ceramide during cisplatin-induced apoptosis in C6 glioma cells. J Neurooncol 2001; 52:11-21.
16) Pecere T, Gazzola MV, Mucignat C, Parolin C, Vecchia FD, Cavaggioni A, Basso G, Diaspro A, Salvato B, Carli M, Palu G. Aloe-emodin is a new type of anticancer agent with selective activity against neuroectodermal tumors. Cancer Res 2000;60:2800-2804.
17) Rang HP, Dale MM: Cancer Chemotherapy. ln: Pharmacology ELBS, Hon-Kong, 1993, pp. 781-803.
18) Saleem R, Faizi S, Deeba F, Sıddıquı BS, Qazi MH. Anthrones from aloe barbadensis. Phytochem 1997;45:1279-1282.
19) Salmon SE, Sartorelli AC. Cancer Chemotherapy. ln: Katzung BG (ed): Basic & Clinical Pharmacology, San Francisco 2001, pp. 923-958.
20) Santini MT, Gabriella R. Three-dimensional spheroid model in tumor biology. Pathobiology 1999;67:148-157.
21) Yeh FT, Wu CH, Lee HZ. Signaling pathway for aloe-emodininduced apoptosis in human H460 lung nonsmall carcinoma cell. Int J Cancer 2003; 106:26-33.