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Power of an Organic Electron Acceptor in Modulation of Intracellular Mitochondrial Reactive Oxygen Species: Inducing JNK- And Caspase-Dependent Apoptosis of Cancer Cells
S. Mohapatra, G. Das, V. Gupta, P. Mondal, M. Nitani, Y. Ie, S. Chatterjee, Y. Aso,
Published in American Chemical Society
2021
Volume: 6
   
Issue: 11
Pages: 7815 - 7828
Abstract
Here, we demonstrate an interesting strategy of modulating mitochondrial reactive oxygen species (ROS) using the organic electron acceptor molecule carbonyl-bridged bithiazole attached with bis-trifluoroacetophenone (BBT). This molecule was found to affect complex I activity. It has the propensity to bind close to the flavin mononucleotide site of complex I of mitochondria where it traps electron released from nicotinamide adenine dinucleotide (NADH) and elevates intracellular ROS, which suggests that the bridged carbonyl in BBT plays a crucial role in the acceptance of electron from NADH. We understand that the potential of the NADH/NAD+ redox couple and low-lying LUMO energy level of BBT are compatible with each other, thus favoring its entrapment of released electrons in complex I. This effect of BBT in ROS generation activates JNK and p38 stress-dependent pathways and resulted in mitochondrial-dependent apoptotic cell death with the reduction in expression of several important cyto-protecting factors (Hsp27 and NFκB), indicating its potential in inhibition of cancer cell relapse. Intriguingly, we found that BBT is not a P-glycoprotein substrate, which further reveals its excellent anticancer potential. This study enlightens us on how the power of electron acceptor ability became an emerging strategy for modulation of intracellular function. © 2021 The Authors. Published by American Chemical Society.
About the journal
JournalData powered by TypesetACS Omega
PublisherData powered by TypesetAmerican Chemical Society
ISSN24701343