Ca<sup>2+</sup>-Dependent Effects of the Selenium-Sorafenib Nanocomplex on Glioblastoma Cells and Astrocytes of the Cerebral Cortex: Anticancer Agent and Cytoprotector
Despite the fact that sorafenib is recommended for the treatment of oncological diseases of the liver, kidneys, and thyroid gland, and recently it has been used for combination therapy of brain cancer of various genesis, there are still significant problems for its widespread and effective use. Amon...
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| Format: | Article |
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MDPI AG
2023-01-01
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| Series: | International Journal of Molecular Sciences |
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| Online Access: | https://www.mdpi.com/1422-0067/24/3/2411 |
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| author | Elena G. Varlamova Venera V. Khabatova Sergey V. Gudkov Egor A. Turovsky |
| author_facet | Elena G. Varlamova Venera V. Khabatova Sergey V. Gudkov Egor A. Turovsky |
| author_sort | Elena G. Varlamova |
| collection | DOAJ |
| description | Despite the fact that sorafenib is recommended for the treatment of oncological diseases of the liver, kidneys, and thyroid gland, and recently it has been used for combination therapy of brain cancer of various genesis, there are still significant problems for its widespread and effective use. Among these problems, the presence of the blood–brain barrier of the brain and the need to use high doses of sorafenib, the existence of mechanisms for the redistribution of sorafenib and its release in the brain tissue, as well as the high resistance of gliomas and glioblastomas to therapy should be considered the main ones. Therefore, there is a need to create new methods for delivering sorafenib to brain tumors, enhancing the therapeutic potential of sorafenib and reducing the cytotoxic effects of active compounds on the healthy environment of tumors, and ideally, increasing the survival of healthy cells during therapy. Using vitality tests, fluorescence microscopy, and molecular biology methods, we showed that the selenium-sorafenib (SeSo) nanocomplex, at relatively low concentrations, is able to bypass the mechanisms of glioblastoma cell chemoresistance and to induce apoptosis through Ca<sup>2+</sup>-dependent induction of endoplasmic reticulum stress, changes in the expression of selenoproteins and selenium-containing proteins, as well as key kinases-regulators of oncogenicity and cell death. Selenium nanoparticles (SeNPs) also have a high anticancer efficacy in glioblastomas, but are less selective, since SeSo in cortical astrocytes causes a more pronounced activation of the cytoprotective pathways. |
| first_indexed | 2024-03-11T09:41:30Z |
| format | Article |
| id | doaj.art-0ef57c6e3ce34d6183ec26f20f3d36b1 |
| institution | Directory Open Access Journal |
| issn | 1661-6596 1422-0067 |
| language | English |
| last_indexed | 2024-03-11T09:41:30Z |
| publishDate | 2023-01-01 |
| publisher | MDPI AG |
| record_format | Article |
| series | International Journal of Molecular Sciences |
| spelling | doaj.art-0ef57c6e3ce34d6183ec26f20f3d36b12023-11-16T16:56:54ZengMDPI AGInternational Journal of Molecular Sciences1661-65961422-00672023-01-01243241110.3390/ijms24032411Ca<sup>2+</sup>-Dependent Effects of the Selenium-Sorafenib Nanocomplex on Glioblastoma Cells and Astrocytes of the Cerebral Cortex: Anticancer Agent and CytoprotectorElena G. Varlamova0Venera V. Khabatova1Sergey V. Gudkov2Egor A. Turovsky3Institute of Cell Biophysics of the Russian Academy of Sciences, Federal Research Center “Pushchino Scientific Center for Biological Research of the Russian Academy of Sciences”, 142290 Pushchino, RussiaProkhorov General Physics Institute of the Russian Academy of Sciences, 38 Vavilove st., 119991 Moscow, RussiaProkhorov General Physics Institute of the Russian Academy of Sciences, 38 Vavilove st., 119991 Moscow, RussiaInstitute of Cell Biophysics of the Russian Academy of Sciences, Federal Research Center “Pushchino Scientific Center for Biological Research of the Russian Academy of Sciences”, 142290 Pushchino, RussiaDespite the fact that sorafenib is recommended for the treatment of oncological diseases of the liver, kidneys, and thyroid gland, and recently it has been used for combination therapy of brain cancer of various genesis, there are still significant problems for its widespread and effective use. Among these problems, the presence of the blood–brain barrier of the brain and the need to use high doses of sorafenib, the existence of mechanisms for the redistribution of sorafenib and its release in the brain tissue, as well as the high resistance of gliomas and glioblastomas to therapy should be considered the main ones. Therefore, there is a need to create new methods for delivering sorafenib to brain tumors, enhancing the therapeutic potential of sorafenib and reducing the cytotoxic effects of active compounds on the healthy environment of tumors, and ideally, increasing the survival of healthy cells during therapy. Using vitality tests, fluorescence microscopy, and molecular biology methods, we showed that the selenium-sorafenib (SeSo) nanocomplex, at relatively low concentrations, is able to bypass the mechanisms of glioblastoma cell chemoresistance and to induce apoptosis through Ca<sup>2+</sup>-dependent induction of endoplasmic reticulum stress, changes in the expression of selenoproteins and selenium-containing proteins, as well as key kinases-regulators of oncogenicity and cell death. Selenium nanoparticles (SeNPs) also have a high anticancer efficacy in glioblastomas, but are less selective, since SeSo in cortical astrocytes causes a more pronounced activation of the cytoprotective pathways.https://www.mdpi.com/1422-0067/24/3/2411sorafenibselenium nanoparticlesselenium–sorafenib nanocomplexglioblastomaastrocytesapoptosis |
| spellingShingle | Elena G. Varlamova Venera V. Khabatova Sergey V. Gudkov Egor A. Turovsky Ca<sup>2+</sup>-Dependent Effects of the Selenium-Sorafenib Nanocomplex on Glioblastoma Cells and Astrocytes of the Cerebral Cortex: Anticancer Agent and Cytoprotector International Journal of Molecular Sciences sorafenib selenium nanoparticles selenium–sorafenib nanocomplex glioblastoma astrocytes apoptosis |
| title | Ca<sup>2+</sup>-Dependent Effects of the Selenium-Sorafenib Nanocomplex on Glioblastoma Cells and Astrocytes of the Cerebral Cortex: Anticancer Agent and Cytoprotector |
| title_full | Ca<sup>2+</sup>-Dependent Effects of the Selenium-Sorafenib Nanocomplex on Glioblastoma Cells and Astrocytes of the Cerebral Cortex: Anticancer Agent and Cytoprotector |
| title_fullStr | Ca<sup>2+</sup>-Dependent Effects of the Selenium-Sorafenib Nanocomplex on Glioblastoma Cells and Astrocytes of the Cerebral Cortex: Anticancer Agent and Cytoprotector |
| title_full_unstemmed | Ca<sup>2+</sup>-Dependent Effects of the Selenium-Sorafenib Nanocomplex on Glioblastoma Cells and Astrocytes of the Cerebral Cortex: Anticancer Agent and Cytoprotector |
| title_short | Ca<sup>2+</sup>-Dependent Effects of the Selenium-Sorafenib Nanocomplex on Glioblastoma Cells and Astrocytes of the Cerebral Cortex: Anticancer Agent and Cytoprotector |
| title_sort | ca sup 2 sup dependent effects of the selenium sorafenib nanocomplex on glioblastoma cells and astrocytes of the cerebral cortex anticancer agent and cytoprotector |
| topic | sorafenib selenium nanoparticles selenium–sorafenib nanocomplex glioblastoma astrocytes apoptosis |
| url | https://www.mdpi.com/1422-0067/24/3/2411 |
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