TY  - JOUR
T1  - GLİOBLASTOMA’da 5-FU ve CELASTROL’ün SİTOTOKSİK ETKİSİ
TT  - THE CYTOTOXIC EFFECT of 5-FU AND CELASTRO L on GLIOBLASTO MA
AU  - Taşpınar, Mehmet
AU  - Denizler, Farika Nur
AU  - Güven, Mustafa
AU  - Yüksek, Veysel
AU  - Çetin, Sedat
AU  - Dede, Semiha
PY  - 2019
DA  - July
JF  - Van Sağlık Bilimleri Dergisi
JO  - Van Sağ Bil Derg
PB  - Van Yüzüncü Yıl Üniversitesi
WT  - DergiPark
SN  - 2667-5072
SP  - 6
EP  - 10
VL  - 11
IS  - 1
LA  - tr
AB  - Glioblastoma (GB), enmalign ve en agresif beyin tümörüdür.Fenotipik ve genotipik açıdan yüksek heterojeniteye sahip Glioblastomanın kesin bir tedavi şekli bulunmamaktadır. Glioblastomadakemoterapi uygulamaları tedavide önemlibir yer tutmaktadır. Ancak kemoterapötik direnç tedavi başarısını düşürmektedir. Kemoterapötik direnci azaltmak ve etkili birkemoterapi iç in bitkiselköken li antikanserojenik mo le küllereliştirilmeye çalışılmaktadır. Son yıllarda, önemlibir tedavi yaklaşımı olara k, bu mo leküllerin tek uygulanmalarının yanında kemoterapötik ajanlarla kombine uygulamaları artmaktadır. Bu çalış mada,kemoterapötik ajan 5-Fluorourac il ile doğal birbileşik olan Ce lastrol kombinasyonunun Glioblastomadaki sitotoksik etkisinin araştırılması amaç lan mıştır.MTT sitotoksisite testi sonucunda 2 µM Celastrolün, 50 µM 5-Fluorouracilin sitotoksik etkisini % 19 oranında arttırdığı, 0,5 ve 2 µM’lık Celastrolün100 µM’lık 5-Fluorouracilin sitotoksik etkisini sırasıyla% 25 ve %37 oranında arttırdığı saptanmıştır. Bu çalış ma, tüm kansertiplerinde 5-Fluorouracilin ile Celastrolün kombine etkisinin gösterildiğ i ilkçalış madır. Celastrolün 5-Fluorouracil ile birlikte kullanımının önemini ilkkez gösteren bu çalışma, yeni bir tedavi protokülünün geliştirilmesi amacıyladaha ileri düzey araştırmalara temel bir dayanak oluşturabilir.
KW  - 5-Florourasil
KW  - Celastrol
KW  - Glioblastoma
KW  - Sitotoksisite
N2  - Glioblastoma is the mostmalign and agressive brain tumor. Glioblastomahas heterogeneityin terms of genotypicallyand phenotypically and alsothere is no precise treatment model. Chemotherapy has a bigrole in the treatment of glioblastoma but chemotherapeutic resistancedecrease the effectiveness of treatment.Anticancerogenic molecules whichderived from plants are devoloping withthe purpose of decreasing chemotheraupatic resistance and effective treatment. In recent years, as animportant treatment approach, the combination of these molecules withchemotherapeutic agents as well as single administration increases. In this study, it was aimed to investigate the cytotoxic effect of the combination of chemotherapeuticagent 5- Fluorouracil and a natural compound Celastrol in glioblastoma.As a result of the MTT cytotoxicity test, it wasdetermined that Celastrol (2µM) has increased the cytotoxic effect of 5- Fluorouracil(50 µM) by 19%, the cytotoxic effect of 5-Fluorouracil (100 µM) has increasedby celastrol (0.5 and 2 µM) inratio of 25% and 37% , respectively.This is the first studyto show the effects of 5-Fluorouracil and celastrol combinationin alltypes of cancer. This study, whichdemonstrated the importance of the use ofcelastrol with 5-Fluorouracil fo r the first time, may provide a basis for further research in order to develop a new treatment protocol
CR  - Acra AM, Sakagami H , Mats uta T , Adachi K, Otsuki S, Nak ajima H ve ark. Effect of thr ee fluor ide compounds on the growth of oral normal and tumor cells. In Vivo.  2012; 26(4) :657-64.
CR  - Blumenthal DT, Sc hulman SF. Survival outco mes in glioblastoma multiforme,including the impact of adj uvant chemot her apy. Expert Rev Neurother . 2005;5(5):683-90.
CR  - Boridy S, Le PU, Petr ecca K, Maysinger D. Celastrol tar gets proteostasis and acts synergistically with a heat-shock protein 90 inhibitor to kill human glioblastoma cells. Cell Death Dis. 2014; 5:e1216.
CR  - Chen M, Rose AE, Doudican N, Osman I, Orlow SJ. Cel astrol synergistically enhances temozolomide cytotoxicity in melanoma cells. Mol Cancer Res. 2009;7(12):1946-53.
CR  - Cloughesy TF, Landolfi J, Hogan DJ, Bloomfield S, Carter  B, Chen   CC,   ve   ark.   Phase   1    trial    of   vocimagene amir etrorepv ec and 5- fluorocytosine for r ecurrent high- grade glioma. Sci Transl Med. 2016;8(341):341ra75.
CR  - Di Cesar e Mannelli L, Piccolo M, Maione F, Ferraro MG, Ir ace C, De Feo V, ve ark. Tanshinones from Salvia miltiorrhiza Bunge revert chemother apy-induc ed neuropathic pain and reduce glioblastoma cells malignancy. Biomed Pharmacother . 2018;105:1042-1049.
CR  - Haar CP, Hebbar P, Wallace GC 4th, Das A, Vandergrift WA 3rd, Smith JA. ve ark. Drug resistance in glioblastoma: a mini review. Neurochem Res. 2012;37(6):1192-200.
CR  - Hanif F, Muzaffar K, Perveen K, Malhi SM, Simjee SU. Glioblastoma Multiforme: A Review of its Epidemiology and Pathogenesis through Clinical Presentation and Treatment. Asian Pac J Cancer Prev. 2017;18(1):3–9.
CR  - Hu Y, Wang S, Wu X, Zhang J, Chen R, Chen M. ve ark. Chinese herbal medicine der ived compounds for cancer therapy: a focus on hepat ocellul ar carcinoma. J Ethnopharmaco l. 2013; 149(3):601-12.
CR  - Kang CW, Park MS, Kim NH, Lee JH , Oh CW, Kim HR, ve ark. Hexane extract from Sar gassum serrat ifo lium inhibits the cell proliferat ion and metast atic ability of human glioblastoma U87MG cells. Oncol Rep. 2015; 34(5): 2602-8.
CR  - Kim SH, Kang JG , Kim CS, Ihm SH, Choi MG, Yoo HJ, v e ark. Cytotoxic effect of celastrol alone or in combination with paclitaxel on anapl astic thyroid carcinoma cells. Tumour Biol. 2017; 39(5):1010428317698369.
CR  - Krex D, Klınk B, Hartmann C, Von Deımlıng A, Pıetsch T, ve ark. Long-term survival with glioblastoma multiforme. Brain: A J Neurol. 2007;130:2596-606.
CR  - Li N, Xu M, Bao N, Shi W, Li Q, Zhang X. v e ark. Discovery of novel NO-r eleasing celastrol derivatives with Hsp90 inhibitio n and cytotoxic act ivities. Eur J Med  Chem. 2018; 160:1-8.
CR  - Menei P, Jadaud E, Faisant N, Boisdron-Celle M, Michalak S, Fournier D, v e ark. Ster eotaxic implantation  of  5- fluorour acil-rel easing micros pher es in mal ignant gl ioma. Cancer. 2004;100(2):405-10.
CR  - Messaoudi K, Clavreul A, Lagarce F. Toward an effective strategy in glioblastoma treatment. Part I: resistance mechanisms and strategies to overcome resistance of glioblastoma to temozolomide. Drug Discov Today. 2015;20(7):899-905.
CR  - Miller CR, Williams CR, Buchsbaum DJ,  Gillespie  GY. Intratumor al 5- fl uorourac il produc ed by cytosine deaminas e/5-fluorocytosine gene ther apy is effective for experimental   human   glioblasto mas.  Canc er   R es. 2002; 62(3):773- 80.
CR  - Nutthasirikul N, Hahnvajanawong C, Techasen A, Limpaiboon T, Leelayuwat C,Chau-In S. ve ark. Tar geting the ∆133p53 isoform can restor e chemosens itivity in 5-fluorour acil- resistant   cholangiocarcinoma  cells.   Int   J    Oncol. 2015; 47(6):2153-64.
CR  - Paolillo M, Boselli C, Schinelli S. Glioblastoma under Siege: An Overview of Curr ent Therapeutic Str ategies . Brain Sci. 2018; 8(1).
CR  - Sander P, Mostafa H, Soboh A, Schneider JM, Pala A, Baron AK ve ark. Vacquinol-1 inducible cell death in glioblastoma multiforme is counter regulated by TRPM7 activity induced by exogenous ATP. Oncotarget. 2017; (21):35124-35137.
CR  - Sat hornsumetee S, Rich JN. Designer therapies for glioblastoma    multiforme.   Ann   N   Y    Acad    Sci. 2008; 1142:108-32.
CR  - Tolba MF, Abdel-Rahman SZ. Pterostilbine, an act ive component of blueberries,sensitizes colon cancer cells to 5-fluorouracil cytotoxicity. Sci Rep. 2015;5: 15239.
CR  - Touat M, Idbaih A, Sanson M, Ligon KL. Glioblastoma targeted therapy: updated approaches from recent biological insights. Ann Oncol. 2017;28(7):1457-1472.
CR  - Uchibor i K, Kasamatsu A, Sunaga M, Yokota S, Sakur ada T, Kobayas hi E. ve ark. Est abl ishment and char acter izat ion of two 5-fl uorouracil-r esist ant hepatoc ellular carcinoma cell l ines. Int J Oncol. 2012; 40(4): 1005-10.
CR  - Wang F, Zheng  Z,  Guan  J, Qi D, Zhou  S,  Shen  X  v e  ark. Ident ificat ion of a panel of genes as a prognostic biomarker for glioblastoma. EBioMedicine.  2018;37:68- 77.
CR  - Wang Z, Zhai Z, Du X. Celastrol inhibits migr ation and invas ion through blocking the NF-κB pathway in ovarian cancer cells . Exp Ther Med. 2017;14(1):819-824.
CR  - Zheng L, Fu Y, Zhuang L, Gai R, Ma J, Lou J. et . al. Simult aneous NF-κB inhibit ion and E-cadherin upregulation mediate mutually synergistic anticancer activity of celastrol and SAHA in vitro and in vivo. Int J Cancer. 2014;135(7):1721- 32.
CR  - Zhu H, Yang W, He LJ, Ding WJ, Zheng L, Liao SD. et al. Upregulating Noxa by ER stress, celastrol exerts synergistic anti-cancer activity in comb ination wit h ABT- 737 in human hepatocellular carcinoma cells. PLo S One. 2012; 7(12):e52333.
UR  - https://dergipark.org.tr/tr/pub/vansaglik/article/588597
L1  - https://dergipark.org.tr/tr/download/article-file/756193
ER  -