Insight into redox regulation of apoptosis in cancer cells with multiparametric live-cell microscopy.

Autor: Shirmanova MV; Privolzhsky Research Medical University, Minin and Pozharsky Sq. 10/1, 603005, Nizhny Novgorod, Russia. shirmanovam@gmail.com., Gavrina AI; Privolzhsky Research Medical University, Minin and Pozharsky Sq. 10/1, 603005, Nizhny Novgorod, Russia., Kovaleva TF; Privolzhsky Research Medical University, Minin and Pozharsky Sq. 10/1, 603005, Nizhny Novgorod, Russia., Dudenkova VV; Privolzhsky Research Medical University, Minin and Pozharsky Sq. 10/1, 603005, Nizhny Novgorod, Russia., Zelenova EE; National Medical Research Radiological Centre of the Ministry of Health of the Russian Federation, 2nd Botkinsky proezd, 3, Moscow, Russia, 125284., Shcheslavskiy VI; Privolzhsky Research Medical University, Minin and Pozharsky Sq. 10/1, 603005, Nizhny Novgorod, Russia.; Becker&Hickl GmbH, Nunsdorfer Ring 7-9, 12277, Berlin, Germany., Mozherov AM; Privolzhsky Research Medical University, Minin and Pozharsky Sq. 10/1, 603005, Nizhny Novgorod, Russia., Snopova LB; Privolzhsky Research Medical University, Minin and Pozharsky Sq. 10/1, 603005, Nizhny Novgorod, Russia., Lukyanov KA; Skolkovo Institute of Science and Technology, Bolshoy Boulevard 30, bld. 1, Moscow, Russia, 121205., Zagaynova EV; Privolzhsky Research Medical University, Minin and Pozharsky Sq. 10/1, 603005, Nizhny Novgorod, Russia.; Lobachevsky State University of Nizhny Novgorod, Gagarin Avenue 23, Nizhny Novgorod, Russia, 603950.
Jazyk: angličtina
Zdroj: Scientific reports [Sci Rep] 2022 Mar 16; Vol. 12 (1), pp. 4476. Date of Electronic Publication: 2022 Mar 16.
DOI: 10.1038/s41598-022-08509-1
Abstrakt: Cellular redox status and the level of reactive oxygen species (ROS) are important regulators of apoptotic potential, playing a crucial role in the growth of cancer cell and their resistance to apoptosis. However, the relationships between the redox status and ROS production during apoptosis remain poorly explored. In this study, we present an investigation on the correlations between the production of ROS, the redox ratio FAD/NAD(P)H, the proportions of the reduced nicotinamide cofactors NADH and NADPH, and caspase-3 activity in cancer cells at the level of individual cells. Two-photon excitation fluorescence lifetime imaging microscopy (FLIM) was applied to monitor simultaneously apoptosis using the genetically encoded sensor of caspase-3, mKate2-DEVD-iRFP, and the autofluorescence of redox cofactors in colorectal cancer cells upon stimulation of apoptosis with staurosporine, cisplatin or hydrogen peroxide. We found that, irrespective of the apoptotic stimulus used, ROS accumulation correlated well with both the elevated pool of mitochondrial, enzyme-bound NADH and caspase-3 activation. Meanwhile, a shift in the contribution of bound NADH could develop independently of the apoptosis, and this was observed in the case of cisplatin. An increase in the proportion of bound NADPH was detected only in staurosporine-treated cells, this likely being associated with a high level of ROS production and their resulting detoxification. The results of the study favor the discovery of new therapeutic strategies based on manipulation of the cellular redox balance, which could help improve the anti-tumor activity of drugs and overcome apoptotic resistance.
(© 2022. The Author(s).)
Databáze: MEDLINE
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