Penetration into Cancer Cells via Clathrin-Dependent Mechanism Allows L-Asparaginase from <i>Rhodospirillum rubrum</i> to Inhibit Telomerase
The anticancer effect of L-asparaginases (L-ASNases) is attributable to their ability to hydrolyze L-asparagine in the bloodstream and cancer cell microenvironment. <i>Rhodospirillum rubrum</i> (RrA) has dual mechanism of action and plays a role in the suppression of telomerase activity....
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MDPI AG
2020-09-01
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| Series: | Pharmaceuticals |
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| Online Access: | https://www.mdpi.com/1424-8247/13/10/286 |
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| author | Anna A. Plyasova Marina V. Pokrovskaya Olga M. Lisitsyna Vadim S. Pokrovsky Svetlana S. Alexandrova Abdullah Hilal Nikolay N. Sokolov Dmitry D. Zhdanov |
| author_facet | Anna A. Plyasova Marina V. Pokrovskaya Olga M. Lisitsyna Vadim S. Pokrovsky Svetlana S. Alexandrova Abdullah Hilal Nikolay N. Sokolov Dmitry D. Zhdanov |
| author_sort | Anna A. Plyasova |
| collection | DOAJ |
| description | The anticancer effect of L-asparaginases (L-ASNases) is attributable to their ability to hydrolyze L-asparagine in the bloodstream and cancer cell microenvironment. <i>Rhodospirillum rubrum</i> (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. |
| first_indexed | 2024-03-10T15:56:26Z |
| format | Article |
| id | doaj.art-fa99e70b503349f1b0ce8c3ecc48e67d |
| institution | Directory Open Access Journal |
| issn | 1424-8247 |
| language | English |
| last_indexed | 2024-03-10T15:56:26Z |
| publishDate | 2020-09-01 |
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| record_format | Article |
| series | Pharmaceuticals |
| spelling | doaj.art-fa99e70b503349f1b0ce8c3ecc48e67d2023-11-20T15:42:38ZengMDPI AGPharmaceuticals1424-82472020-09-01131028610.3390/ph13100286Penetration into Cancer Cells via Clathrin-Dependent Mechanism Allows L-Asparaginase from <i>Rhodospirillum rubrum</i> to Inhibit TelomeraseAnna A. Plyasova0Marina V. Pokrovskaya1Olga M. Lisitsyna2Vadim S. Pokrovsky3Svetlana S. Alexandrova4Abdullah Hilal5Nikolay N. Sokolov6Dmitry D. Zhdanov7Institute of Biomedical Chemistry, Pogodinskaya st. 10/8, 119121 Moscow, RussiaInstitute of Biomedical Chemistry, Pogodinskaya st. 10/8, 119121 Moscow, RussiaInternational Biotechnology Center “Generium” LLC, Vladimirskaya st. 14, 601125 Volginsky, RussiaN.N. Blokhin Cancer Research Center, Kashirskoe Shosse 24, 115478 Moscow, RussiaInstitute of Biomedical Chemistry, Pogodinskaya st. 10/8, 119121 Moscow, RussiaInstitute of Biomedical Chemistry, Pogodinskaya st. 10/8, 119121 Moscow, RussiaInstitute of Biomedical Chemistry, Pogodinskaya st. 10/8, 119121 Moscow, RussiaInstitute of Biomedical Chemistry, Pogodinskaya st. 10/8, 119121 Moscow, RussiaThe anticancer effect of L-asparaginases (L-ASNases) is attributable to their ability to hydrolyze L-asparagine in the bloodstream and cancer cell microenvironment. <i>Rhodospirillum rubrum</i> (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.https://www.mdpi.com/1424-8247/13/10/286<i>Rhodospirillum rubrum</i>L-asparaginasetelomeraseendocytosisclathrindynamin |
| spellingShingle | Anna A. Plyasova Marina V. Pokrovskaya Olga M. Lisitsyna Vadim S. Pokrovsky Svetlana S. Alexandrova Abdullah Hilal Nikolay N. Sokolov Dmitry D. Zhdanov Penetration into Cancer Cells via Clathrin-Dependent Mechanism Allows L-Asparaginase from <i>Rhodospirillum rubrum</i> to Inhibit Telomerase Pharmaceuticals <i>Rhodospirillum rubrum</i> L-asparaginase telomerase endocytosis clathrin dynamin |
| title | Penetration into Cancer Cells via Clathrin-Dependent Mechanism Allows L-Asparaginase from <i>Rhodospirillum rubrum</i> to Inhibit Telomerase |
| title_full | Penetration into Cancer Cells via Clathrin-Dependent Mechanism Allows L-Asparaginase from <i>Rhodospirillum rubrum</i> to Inhibit Telomerase |
| title_fullStr | Penetration into Cancer Cells via Clathrin-Dependent Mechanism Allows L-Asparaginase from <i>Rhodospirillum rubrum</i> to Inhibit Telomerase |
| title_full_unstemmed | Penetration into Cancer Cells via Clathrin-Dependent Mechanism Allows L-Asparaginase from <i>Rhodospirillum rubrum</i> to Inhibit Telomerase |
| title_short | Penetration into Cancer Cells via Clathrin-Dependent Mechanism Allows L-Asparaginase from <i>Rhodospirillum rubrum</i> to Inhibit Telomerase |
| title_sort | penetration into cancer cells via clathrin dependent mechanism allows l asparaginase from i rhodospirillum rubrum i to inhibit telomerase |
| topic | <i>Rhodospirillum rubrum</i> L-asparaginase telomerase endocytosis clathrin dynamin |
| url | https://www.mdpi.com/1424-8247/13/10/286 |
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