A comparison of the inhibitory effects of anti-cancer drugs on thioredoxin reductase and glutathione S-transferase in rat liver
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Tarih
2018
Dergi Başlığı
Dergi ISSN
Cilt Başlığı
Yayıncı
Bentham Science
Erişim Hakkı
info:eu-repo/semantics/closedAccess
Özet
Background: 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.
Açıklama
Anahtar Kelimeler
Anticancer Drug, Inhibition, Molecular Docking, Thioredoxin Reductase, Glutathione S-Transferase, Rat Liver
Kaynak
Anti-Cancer Agents in Medicinal Chemistry
WoS Q Değeri
N/A
Scopus Q Değeri
Q2
Cilt
18
Sayı
14
