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Penetration into Cancer Cells via Clathrin-Dependent Mechanism Allows L-Asparaginase from Rhodospirillum rubrum to Inhibit Telomerase

1
Institute of Biomedical Chemistry, Pogodinskaya st. 10/8, 119121 Moscow, Russia
2
International Biotechnology Center “Generium” LLC, Vladimirskaya st. 14, 601125 Volginsky, Russia
3
N.N. Blokhin Cancer Research Center, Kashirskoe Shosse 24, 115478 Moscow, Russia
4
Department of Biochemistry, Рeoples Friendship University of Russia (RUDN University), Miklukho-Maklaya st. 6, 117198 Moscow, Russia
*
Author to whom correspondence should be addressed.
Pharmaceuticals 2020, 13(10), 286; https://doi.org/10.3390/ph13100286
Received: 2 September 2020 / Revised: 21 September 2020 / Accepted: 28 September 2020 / Published: 30 September 2020
(This article belongs to the Special Issue Amino Acids Metabolism and Cancer Therapy)
The anticancer effect of L-asparaginases (L-ASNases) is attributable to their ability to hydrolyze L-asparagine in the bloodstream and cancer cell microenvironment. Rhodospirillum rubrum (RrA) has dual mechanism of action and plays a role in the suppression of telomerase activity. The aim of this work was to investigate the possible mechanism of RrA penetration into human cancer cells. Labeling of widely used L-ASNases by fluorescein isothiocyanate followed by flow cytometry and fluorescent microscopy demonstrated that only RrA can interact with cell membranes. The screening of inhibitors of receptor-mediated endocytosis demonstrated the involvement of clathrin receptors in RrA penetration into cells. Confocal microscopy confirmed the cytoplasmic and nuclear localization of RrA in human breast cancer SKBR3 cells. Two predicted nuclear localization motifs allow RrA to penetrate into the cell nucleus and inhibit telomerase. Chromatin relaxation promoted by different agents can increase the ability of RrA to suppress the expression of telomerase main catalytic subunit. Our study demonstrated for the first time the ability of RrA to penetrate into human cancer cells and the involvement of clathrin receptors in this process. View Full-Text
Keywords: Rhodospirillum rubrum; L-asparaginase; telomerase; endocytosis; clathrin; dynamin Rhodospirillum rubrum; L-asparaginase; telomerase; endocytosis; clathrin; dynamin
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MDPI and ACS Style

Plyasova, A.A.; Pokrovskaya, M.V.; Lisitsyna, O.M.; Pokrovsky, V.S.; Alexandrova, S.S.; Hilal, A.; Sokolov, N.N.; Zhdanov, D.D. Penetration into Cancer Cells via Clathrin-Dependent Mechanism Allows L-Asparaginase from Rhodospirillum rubrum to Inhibit Telomerase. Pharmaceuticals 2020, 13, 286. https://doi.org/10.3390/ph13100286

AMA Style

Plyasova AA, Pokrovskaya MV, Lisitsyna OM, Pokrovsky VS, Alexandrova SS, Hilal A, Sokolov NN, Zhdanov DD. Penetration into Cancer Cells via Clathrin-Dependent Mechanism Allows L-Asparaginase from Rhodospirillum rubrum to Inhibit Telomerase. Pharmaceuticals. 2020; 13(10):286. https://doi.org/10.3390/ph13100286

Chicago/Turabian Style

Plyasova, Anna A., Marina V. Pokrovskaya, Olga M. Lisitsyna, Vadim S. Pokrovsky, Svetlana S. Alexandrova, Abdullah Hilal, Nikolay N. Sokolov, and Dmitry D. Zhdanov. 2020. "Penetration into Cancer Cells via Clathrin-Dependent Mechanism Allows L-Asparaginase from Rhodospirillum rubrum to Inhibit Telomerase" Pharmaceuticals 13, no. 10: 286. https://doi.org/10.3390/ph13100286

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