Abstract
Introduction. Despite the available data on tumor cell functioning under the conditions of free radical-mediated oxidation, the mechanisms of redox regulation, cell proliferation management and apoptosis avoidance remain understudied. The objective of the study was to identify the role of the thioredoxin system in regulating MCF-7 breast cancer cell proliferation under redox status modulation with 1.4-dithioerythritol. Material and methods. The studies were conducted on the MCF-7 breast cancer cell line, grown in adherent cell culture. Cell redox status was modulated with5 mM N-ethylmaleimide – an SH group and peptide inhibitor and5 mM 1.4-dithioerythritol – a thiol group protector. The cell cycle was evaluated by flow cytometry, the same technique was used to measure the reactive oxygen species concentration. The levels of reduced and oxidized glutathione and the activity of thioredoxin reductase were identified by spectrophotometry. The intracellular concentrations of thioredoxin, cyclin E and cyclin-dependent kinase 2 were determined by Western blot analysis. Results and discussion. The essential role of the thioredoxin system in regulating MCF-7 breast cancer cell proliferation was exhibited. S-phase arrest under the effect of N-ethylmaleimide and G0/G1-phase arrest under the effect of 1.4-dithioerythritol are associated with the changes in the activity of redox-sensitive protein complexes (cyclins and cyclin-dependent kinases) that regulate cell proliferation. Conclusion. Redoxdependent modulation of proliferation regulating intracellular protein activity occurs due to the thioredoxin system. This is a promising research area for seeking molecular targets of breast cell malignization.
Highlights
Despite the available data on tumor cell functioning under the conditions of free radical-mediated oxidation, the mechanisms of redox regulation, cell proliferation management and apoptosis avoidance remain understudied
The studies were conducted on the MCF-7 breast cancer cell line, grown in adherent cell culture
Cell redox status was modulated with 5 mM N-ethylmaleimide – an SH group and peptide inhibitor - and 5 mM 1.4-dithioerythritol – a thiol group protector
Summary
СИСТЕМА ТИОРЕДОКСИНА В РЕГУЛЯЦИИ ПРОЛИФЕРАЦИИ КЛЕТОК ЛИНИИ MCF-7 ПРИ МОДУЛЯЦИИ РЕДОКС-СТАТУСА. Цель исследования – выявить участие системы тиоредоксина в регуляции пролиферации клеток аденокарциномы молочной железы линии МСF-7 при модуляции редокс-статуса блокатором SH-групп белков и пептидов N-этилмалеимидом и протектором тиоловых групп – 1,4-дитиоэритритолом. Показана важная роль системы тиоредоксина в регуляции пролиферации клеток линии МСF-7. Редокс-зависимая модуляция функционирования внутриклеточных белков, регулирующих пролиферацию, осуществляется при участии системы тиоредоксина. Активация свободно-радикального окисления с продукцией активных форм кислорода (АФК) в опухолевых клетках молочной железы приводит к повреждению макромолекул, в частности белков, участвующих в регуляции пролиферации и программированной клеточной гибели [1–6]. В поддержании внутриклеточного редокс-гомеостаза важную роль играют системы глутатиона, тиоредоксина, глутаредоксина и другие, функционирование которых приводит к снижению уровня АФК, изменению активности факторов транскрипции и экспрессии ряда генов при адаптивных реакциях клеток на изменяющиеся условия [1, 6, 7].
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