Isoimperatorin-Mediated Anticancer Activity: Role Of Mitochondrial Dysfunction ‘n Hepg2 Cells
Küçük Resim Yok
Tarih
2023
Dergi Başlığı
Dergi ISSN
Cilt Başlığı
Yayıncı
University of Ankara
Erişim Hakkı
info:eu-repo/semantics/openAccess
Özet
Objective: The first goal of the present study is to investigate the role of mitochondria due to the Crabtree effect in HepG2 cells exposed to ISO in either glucose-or galactose-conditioned media. The second aim is to predict the interactions between electron transport chain (ETC) complexes and ISO, which might be the possible reason for mitochondrial dysfunction. Material and Method: Cell viability and membrane damage for HepG2 cells exposed to ISO (12.5, 25, 50, 100, and 250 uM) were assessed by MTT and LDH leakage assays in either glucose-or galactose-conditioned media. The affinity of ISO to ETC complexes was also determined by a molecular docking study. Result and Discussion: MTT assay showed that 250 uM ISO leads to cytotoxic activity in glucose-conditioned media, while 25 uM and higher concentrations of ISO decrease cell viability in galactose-conditioned media. A membrane damage assay conducted in a glucose-conditioned media assay revealed that 250 uM ISO disrupts the cell membrane. 100 and 250 uM ISO increased membrane damage in galactose-conditioned media. According to docking simulations, binding affinities of ISO to ETC complexes are in descending order: Complex IV Complex I Complex III Complex II. Inhibition of complex IV by ISO inhibits the transfer of electrons from cytochrome c to oxygen, and the proton gradient collapses. The present study proposed that ISO leads to mitochondrial dysfunction via inhibition of the ETC. © 2023 University of Ankara. All rights reserved.
Açıklama
Anahtar Kelimeler
Anticancer, crabtree effect, electron transport chain, isoimperatorin, mitochondrial dysfunction, cytochrome c, cytochrome c oxidase, galactose, glucose, isoimperatorin, lactate dehydrogenase, oxygen, proton, reduced nicotinamide adenine dinucleotide dehydrogenase (ubiquinone), succinate dehydrogenase (ubiquinone), ubiquinol cytochrome c reductase, antineoplastic activity, Article, binding affinity, cell membrane, cell viability, controlled study, Crabtree effect, cytolysis assay, disorders of mitochondrial functions, drug cytotoxicity, drug protein binding, electron transport, enzyme inhibition, Hep-G2 cell line, human, human cell, ligand binding, liver cell carcinoma, liver mitochondrion, membrane damage, molecular docking, MTT assay, respiratory chain
Kaynak
Ankara Universitesi Eczacilik Fakultesi Dergisi
WoS Q Değeri
Scopus Q Değeri
N/A
Cilt
47
Sayı
3
