Buradasınız

C6 SIÇAN GLİOMA HÜCRELERİ ÜZERİNE ALOE EMODİN VE CİSPLATININ ETKİLERİNİN İKİ VE ÜÇ BOYUTLU HÜCRE KÜLTÜR MODELLERİNDE İNCELENMESİ

THE EFFECTS OF ALOE EMODIN AND CISPLATIN ON RAT GLIOMA CELL LINE IN TWO AND THREE-DIMENSIONAL CELL CULTURE MODELS

Journal Name:

Publication Year:

Author NameUniversity of AuthorFaculty of Author
Abstract (2. Language): 
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<0.0125). Aloe emodin has also reduced S-phase labeling in three-dimensional cell culture (p<0.0125). No significant disruption has been detected in spheroid morphology. Cisplatin has reduced cell proliferation and S-phase fraction in two-dimensional cell culture to a greater extent when compared to aloe emodin. Cisplatin also decreased S-phase labeling index in three-dimensional cell culture significantly when compared to other groups. The overall morphology of the spheroids was observed to be more strongly destroyed compared to aloe emodin and control groups. The findings obtained by administrating the combination of both drugs in two and three-dimensional cultures were similar to those of the cisplatin group.Conclusion: In conclusion, the combination of aloe emodin and cisplatin decreases cell proliferation and S-phase fraction and causes disruption of the morphology of C6 glioma cells in two- and three-dimensional cell culture models, but no aggravation or alleviation of the effects of cisplatin can be observed by aloe emodin treatment.
Abstract (Original Language): 
Amaç: Bu çal›flman›n amac›, do¤al bir antrakinon türevi olan aloe emodin ve organoplatinler grubundan kemoteropatik bir ilaç olan cisplatinin ayr› ayr› ve birarada kullan›ld›klar›nda C6 glioma hücre soyu üzerine etkilerini iki ve üç boyutlu tümör hücre kültür modelleri kullan›larak incelemekti. Gereç ve yöntem: ‹ki boyutlu kültürlerde iki ilac›n ayr› ayr› ve birlikte kullan›mlar› 12, 24, 48, 72. saatlerde hem hücre ço¤almas›, hem de hücre siklusu sentez faz› aç›s›ndan incelendi. Üç boyutlu hücre kültürü modelinde ise her iki ilac›n ayr› ayr› ve kombine kullan›mlar› 72. saatte hücre siklusu sentez faz› ve hücre ince yap›s› aç›s›ndan de- ¤erlendirildi. Bulgular: Aloe emodin, iki boyutlu kültürde hücre ço¤almas›n› azalt›c› etki gösterdi ve hücre siklusu sentez faz› iflaretlenmesinde azalma meydana getirdi (p<0,0125). Üç boyutlu kültürde de sentez faz›nda azalmaya yol açt›¤› görüldü (p<0,0125). Sferoid morfolojisinde belirgin bir bozukluk tespit edilmedi. Cisplatin de iki boyutlu kültürde hücre ço¤almas›n› azaltt› ve hücre siklusu sentez faz› iflaretlenmesinde daha belirgin azalma meydana getirdi (p<0,0125). Üç boyutlu kültürde de sentez faz›nda daha etkin azalmaya yol açt›¤› görüldü (p<0,0125). Sferoidlerin genel morfolojileri kontrol ve aloe emodin grubuna göre bozuktu. Kombinasyon grubunda iki ve üç boyutlu kültürlerde elde edilen bulgular cisplatin grubunda elde edilen bulgularla benzerdi. Sonuç: Aloe emodin ve cisplatin kombine uyguland›klar›nda C6 glioma hücreleri üzerine etkileri iki ve üç boyutlu kültür modellerinde incelendi¤inde hücre siklusunda sentez faz›ndaki hücrelerin say›s›nda azalmaya yol açarak hücre proliferasyonunu azaltt›¤› ve hücre yap›s›nda bozulmaya yol açt›¤› gözlendi. Ancak aloe emodinin cisplatinin etkisini artt›r›c› ya da azalt›c› yönde bir etkisinin bulunmad›¤› da tespit edildi.
110-116

REFERENCES

References: 

1. Algier LA., Hano¤lu 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. Krajc› 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, S›dd›qu› 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.

Thank you for copying data from http://www.arastirmax.com