Response of Human Glioblastoma Cells to Vitamin B12 Deficiency: A Study Using the Non-Toxic Cobalamin Antagonist
The most important biological function of vitamin B12 is to accomplish DNA synthesis, which is necessary for cell division. Cobalamin deficiency may be especially acute for rapidly dividing cells, such as glioblastoma cells. Therefore, cobalamin antagonists offer a medicinal potential for developing...
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doaj-819e78847c9f4d84817646ac5d0b87e92021-01-20T00:04:16ZengMDPI AGBiology2079-77372021-01-0110696910.3390/biology10010069Response of Human Glioblastoma Cells to Vitamin B12 Deficiency: A Study Using the Non-Toxic Cobalamin AntagonistZuzanna Rzepka0Jakub Rok1Mateusz Maszczyk2Artur Beberok3Justyna Magdalena Hermanowicz4Dariusz Pawlak5Dorota Gryko6Dorota Wrześniok7Department of Pharmaceutical Chemistry, Faculty of Pharmaceutical Sciences in Sosnowiec, Medical University of Silesia in Katowice, Jagiellońska 4, 41-200 Sosnowiec, PolandDepartment of Pharmaceutical Chemistry, Faculty of Pharmaceutical Sciences in Sosnowiec, Medical University of Silesia in Katowice, Jagiellońska 4, 41-200 Sosnowiec, PolandDepartment of Pharmaceutical Chemistry, Faculty of Pharmaceutical Sciences in Sosnowiec, Medical University of Silesia in Katowice, Jagiellońska 4, 41-200 Sosnowiec, PolandDepartment of Pharmaceutical Chemistry, Faculty of Pharmaceutical Sciences in Sosnowiec, Medical University of Silesia in Katowice, Jagiellońska 4, 41-200 Sosnowiec, PolandDepartment of Pharmacodynamics, Medical University of Bialystok, Mickiewicza 2C, 15-222 Bialystok, PolandDepartment of Pharmacodynamics, Medical University of Bialystok, Mickiewicza 2C, 15-222 Bialystok, PolandInstitute of Organic Chemistry, Polish Academy of Science, Kasprzaka 44/52, 01-224 Warsaw, PolandDepartment of Pharmaceutical Chemistry, Faculty of Pharmaceutical Sciences in Sosnowiec, Medical University of Silesia in Katowice, Jagiellońska 4, 41-200 Sosnowiec, PolandThe most important biological function of vitamin B12 is to accomplish DNA synthesis, which is necessary for cell division. Cobalamin deficiency may be especially acute for rapidly dividing cells, such as glioblastoma cells. Therefore, cobalamin antagonists offer a medicinal potential for developing anti-glioma agents. In the present study, we developed an in vitro model of cobalamin deficiency in glioblastoma cells. Long-term treatment of cells with the cobalamin analogue, hydroxycobalamin [<i>c</i>-lactam] (HCCL) was applied to induce an increase of hypocobalaminemia biomarker. Cytometric assays demonstrated that vitamin B12 promoted glioblastoma cells proliferation, whereas the treatment of cells with HCCL caused a dramatic inhibition of cell proliferation and an induction of cell cycle arrest at the G2/M phase. Vitamin B12 counteracted all the observed effects of HCCL. In the in silico study, we characterized the molecular interactions between HCCL and transcobalamin II (TCII). We have demonstrated that HCCL shares similar interactions with TCII as naturally occurring cobalamins and therefore may act as a competitive inhibitor of this key transporter protein. We assessed the impact of HCCL on the mortality or developmental malformations of zebrafish embryos. Collectively, our findings suggest that the use of cobalamin transport antagonists as potential anti-glioma agents would be worth exploring further.https://www.mdpi.com/2079-7737/10/1/69cobalaminvitamin B12glioblastomavitamin B12 deficiencyantivitaminscobalamin antagonists |
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DOAJ |
language |
English |
format |
Article |
sources |
DOAJ |
author |
Zuzanna Rzepka Jakub Rok Mateusz Maszczyk Artur Beberok Justyna Magdalena Hermanowicz Dariusz Pawlak Dorota Gryko Dorota Wrześniok |
spellingShingle |
Zuzanna Rzepka Jakub Rok Mateusz Maszczyk Artur Beberok Justyna Magdalena Hermanowicz Dariusz Pawlak Dorota Gryko Dorota Wrześniok Response of Human Glioblastoma Cells to Vitamin B12 Deficiency: A Study Using the Non-Toxic Cobalamin Antagonist Biology cobalamin vitamin B12 glioblastoma vitamin B12 deficiency antivitamins cobalamin antagonists |
author_facet |
Zuzanna Rzepka Jakub Rok Mateusz Maszczyk Artur Beberok Justyna Magdalena Hermanowicz Dariusz Pawlak Dorota Gryko Dorota Wrześniok |
author_sort |
Zuzanna Rzepka |
title |
Response of Human Glioblastoma Cells to Vitamin B12 Deficiency: A Study Using the Non-Toxic Cobalamin Antagonist |
title_short |
Response of Human Glioblastoma Cells to Vitamin B12 Deficiency: A Study Using the Non-Toxic Cobalamin Antagonist |
title_full |
Response of Human Glioblastoma Cells to Vitamin B12 Deficiency: A Study Using the Non-Toxic Cobalamin Antagonist |
title_fullStr |
Response of Human Glioblastoma Cells to Vitamin B12 Deficiency: A Study Using the Non-Toxic Cobalamin Antagonist |
title_full_unstemmed |
Response of Human Glioblastoma Cells to Vitamin B12 Deficiency: A Study Using the Non-Toxic Cobalamin Antagonist |
title_sort |
response of human glioblastoma cells to vitamin b12 deficiency: a study using the non-toxic cobalamin antagonist |
publisher |
MDPI AG |
series |
Biology |
issn |
2079-7737 |
publishDate |
2021-01-01 |
description |
The most important biological function of vitamin B12 is to accomplish DNA synthesis, which is necessary for cell division. Cobalamin deficiency may be especially acute for rapidly dividing cells, such as glioblastoma cells. Therefore, cobalamin antagonists offer a medicinal potential for developing anti-glioma agents. In the present study, we developed an in vitro model of cobalamin deficiency in glioblastoma cells. Long-term treatment of cells with the cobalamin analogue, hydroxycobalamin [<i>c</i>-lactam] (HCCL) was applied to induce an increase of hypocobalaminemia biomarker. Cytometric assays demonstrated that vitamin B12 promoted glioblastoma cells proliferation, whereas the treatment of cells with HCCL caused a dramatic inhibition of cell proliferation and an induction of cell cycle arrest at the G2/M phase. Vitamin B12 counteracted all the observed effects of HCCL. In the in silico study, we characterized the molecular interactions between HCCL and transcobalamin II (TCII). We have demonstrated that HCCL shares similar interactions with TCII as naturally occurring cobalamins and therefore may act as a competitive inhibitor of this key transporter protein. We assessed the impact of HCCL on the mortality or developmental malformations of zebrafish embryos. Collectively, our findings suggest that the use of cobalamin transport antagonists as potential anti-glioma agents would be worth exploring further. |
topic |
cobalamin vitamin B12 glioblastoma vitamin B12 deficiency antivitamins cobalamin antagonists |
url |
https://www.mdpi.com/2079-7737/10/1/69 |
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