FEATURES OF REDOX REGULATION IN TUMOR CELLS
Nikolay Konstantinovich ZENKOV1, Peter Mikhaylovich KOZHIN1, Aleksandra Vasil’evna VCHERASHNYAYA2, Grigory Grigor'evich MARTINOVICH2, Natal’ya Valer’evna KANDALINTSEVA3, Elena Bronislavovna MENSHCHIKOVA1
1Research Institute for Experimental and Clinical and Medicine, Federal Research Center for Fundamental and Translational Medicine
2Belarusian State University
3Novosibirsk State Pedagogical University
Keywords: активированные кислородные метаболиты (АКМ), антиоксиданты, митохондрии, NAD(P)H-оксидазы, опухоль, reactive oxygen (ROS) and nitrogen species, antioxidants, mitochondria, NAD(P)H oxidases, tumor
Abstract
Endogenous mechanisms of reactive oxygen (ROS) and nitrogen species production and of antioxidant defense systems in tumor cells are analyzed. Increased ROS production is an important regulator of metabolic changes in these cells: enhanced proliferation, apoptosis inhibition, resistance to hypoxia and to cytostatics (doxorubicin, carboplatin, cisplatin, etc.). The most active ROS sources in tumor cells are mitochondria, NAD(P)H oxidases and peroxisomes, which synthesize O2·- and H2O2. In mitochondria, the superoxide anion radical is generated mainly by complexes I and III; membrane NAD(P)H oxidases Nox1, Nox2, Nox3, and Nox5 produce O2·-, Nox4, and dual oxidases DUOX-1, DUOX-2 - mainly H2O2. Increasing ROS stationary concentration activates endogenous antioxidant defense mechanisms, such as redox-dependent antioxidant respons(iv)e element system Keap1/Nrf2/ARE and autophagy, which allows tumor cells to survive under oxidative stress and may underlie resistance to radio- and chemotherapy. The possibilities of tumor cell redox balance regulation by antioxidants with targeted action and by specific inhibitors of ROS enzymatic production are discussed.
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