A comparison of the inhibitory effects of anti-cancer drugs on thioredoxin reductase and glutathione S-transferase in rat liver

Basit Öğe Kaydı
dc.authoridderyanur -- 0000-0002-9115-136X
dc.contributor.authorÖzgençli, İlknur
dc.contributor.authorKılıç, Deryanur
dc.contributor.authorGüller, Uğur
dc.contributor.authorÇiftçi, Mehmet
dc.contributor.authorKüfrevioğlu, Ömer İrfan
dc.contributor.authorBudak, Harun
dc.date.accessioned13.07.201910:50:10
dc.date.accessioned2019-07-16T09:17:31Z
dc.date.available13.07.201910:50:10
dc.date.available2019-07-16T09:17:31Z
dc.date.issued2018
dc.departmentFen-Edebiyat Fakültesi
dc.description.abstractBackground: While Thioredoxin Reductase (TrxR) plays an important role in regulation of the intracellular redox balance and various signalling pathways, Glutathione S-Transferase (GSTs) enzymes belong to the detoxification family that catalyse the conjugation of glutathione with various endogenous and xenobiotic electrophiles. Since TrxR and GSTs are overexpressed in many cancer cells, they have been identified as potential targets to develop chemotherapeutic strategies. Method: The mitochondrial TrxR (TrxR2) enzyme and the cytosolic CYST enzyme was purified from rat liver via affinity chromatography. After the purification, the in vitro inhibition effects of some anticancer drugs (cisplatin, calcium folinate, carboplatin, epirubicin hydrochloride, doxorubicin hydrochloride, paclitaxel, etoposide, fluorouracil, and methotrexate) were investigated on both enzymes. Since only methotrexate inhibits both enzymes among all the anticancer drugs, a molecular docking study was performed to determine the binding site and the binding affinity of methotrexate to the enzymes. Results: Firstly, TrxR2 and GST were found to have a specific activity of 0.436, 1765 EU/mg proteins with a yield of 39.20%, 31.28% and 207.6, 3516.6 of purification fold, respectively. While TrxR2 was strongly inhibited by all of the anticancer drugs, GST was not inhibited by any of the anticancer drugs except methotrexate. Conclusion: Both enzymes were inhibited by only methotrexate in rat liver, and methotrexate was well placed in the active sites of both proteins. Therefore, it may be argued that methotrexate may be a more effective anticancer drug than all other drugs used in this study against the multi drug resistance that will occur during chemotherapy.
dc.description.sponsorshipAtaturk University Scientific Research Projects Coordination Commission (ATAUNIBAP) [PRJ2015/97, PRJ2015/357]
dc.description.sponsorshipThis work was financially supported by Ataturk University Scientific Research Projects Coordination Commission (ATAUNIBAP) with project number PRJ2015/97 and PRJ2015/357. The author(s) have no potential conflict of interest with respect to the research, authorship, and/or publication of this article. Conceived and designed the experiments: Harun Budak (group leader) and Ilknur Ozgencli. Performed the experiments: Harun Budak, Ilknur Ozgencli, Deryanur Kilic, Ugur Guller, Mehmet Ciftci, and Omer I. Kufrevioglu. Analysed the data: Harun Budak, Ilknur Ozgencli, Deryanur Kilic, and Ugur Guller. Contributed reagents/materials/analysis tools: Harun Budak. Wrote the paper: Harun Budak, Ilknur Ozgencli, Deryanur Kilic, and Ugur Guller. All authors read and approved the final manuscript.
dc.identifier.doi10.2174/1871520618666180910093335
dc.identifier.endpage2061en_US
dc.identifier.issn1871-5206
dc.identifier.issn1875-5992
dc.identifier.issue14en_US
dc.identifier.pmid30198440
dc.identifier.scopusqualityQ2
dc.identifier.startpage2053en_US
dc.identifier.urihttps://doi.org/10.2174/1871520618666180910093335
dc.identifier.urihttps://hdl.handle.net/20.500.12451/4760
dc.identifier.volume18en_US
dc.identifier.wosWOS:000458732100013
dc.identifier.wosqualityN/A
dc.indekslendigikaynakWeb of Science
dc.indekslendigikaynakScopus
dc.indekslendigikaynakPubMed
dc.language.isoen
dc.publisherBentham Science
dc.relation.ispartofAnti-Cancer Agents in Medicinal Chemistry
dc.relation.publicationcategoryMakale - Uluslararası Hakemli Dergi - Kurum Öğretim Elemanı
dc.rightsinfo:eu-repo/semantics/closedAccess
dc.subjectAnticancer Drug
dc.subjectInhibition
dc.subjectMolecular Docking
dc.subjectThioredoxin Reductase
dc.subjectGlutathione S-Transferase
dc.subjectRat Liver
dc.titleA comparison of the inhibitory effects of anti-cancer drugs on thioredoxin reductase and glutathione S-transferase in rat liver
dc.typeArticle

Dosyalar

Koleksiyon

Makale Koleksiyonu
PubMed İndeksli Yayınlar Koleksiyonu
Scopus İndeksli Yayınlar Koleksiyonu
WoS İndeksli Yayınlar Koleksiyonu