ISOIMPERATORIN-MEDIATED ANTICANCER ACTIVITY: ROLE OF MITOCHONDRIAL DYSFUNCTION IN HEPG2 CELLS

Authors : Ali ERGÜÇ, Ege ARZUK, Gökay ALBAYRAK, Fuat KARAKUŞ, Hayati OKUR, Şüra BAYKAN

Pages : 836-844

Doi:10.33483/jfpau.1312637

View : 107 | Download : 100

Publication Date : 2023-09-20

Article Type : Research Paper

Abstract :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 insert ignore into journalissuearticles values(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 insert ignore into journalissuearticles values(12.5, 25, 50, 100, and 250 µM); 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 µM ISO leads to cytotoxic activity in glucose-conditioned media, while 25 µM 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 µM ISO disrupts the cell membrane. 100 and 250 µM 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.
Keywords : Antikanser, crabtree etkisi, elektron transfer zinciri, izoimperatorin, mitokondriyal disfonksiyon