Implications of Oxidative Stress in Glioblastoma Multiforme Following Treatment with Purine Derivatives
Recently, small compound-based therapies have provided new insights into the treatment of glioblastoma multiforme (GBM) by inducing oxidative impairment. Kinetin riboside (KR) and newly designed derivatives (8-azaKR, 7-deazaKR) selectively affect the molecular pathways crucial for cell growth by int...
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| Format: | Article |
| Language: | English |
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MDPI AG
2021-06-01
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| Series: | Antioxidants |
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| Online Access: | https://www.mdpi.com/2076-3921/10/6/950 |
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| author | Marta Orlicka-Płocka Agnieszka Fedoruk-Wyszomirska Dorota Gurda-Woźna Paweł Pawelczak Patrycja Krawczyk Małgorzata Giel-Pietraszuk Grzegorz Framski Tomasz Ostrowski Eliza Wyszko |
| author_facet | Marta Orlicka-Płocka Agnieszka Fedoruk-Wyszomirska Dorota Gurda-Woźna Paweł Pawelczak Patrycja Krawczyk Małgorzata Giel-Pietraszuk Grzegorz Framski Tomasz Ostrowski Eliza Wyszko |
| author_sort | Marta Orlicka-Płocka |
| collection | DOAJ |
| description | Recently, small compound-based therapies have provided new insights into the treatment of glioblastoma multiforme (GBM) by inducing oxidative impairment. Kinetin riboside (KR) and newly designed derivatives (8-azaKR, 7-deazaKR) selectively affect the molecular pathways crucial for cell growth by interfering with the redox status of cancer cells. Thus, these compounds might serve as potential alternatives in the oxidative therapy of GBM. The increased basal levels of reactive oxygen species (ROS) in GBM support the survival of cancer cells and cause drug resistance. The simplest approach to induce cell death is to achieve the redox threshold and circumvent the antioxidant defense mechanisms. Consequently, cells become more sensitive to oxidative stress (OS) caused by exogenous agents. Here, we investigated the effect of KR and its derivatives on the redox status of T98G cells in 2D and 3D cell culture. The use of spheroids of T98G cells enabled the selection of one derivative—7-deazaKR—with comparable antitumor activity to KR. Both compounds induced ROS generation and genotoxic OS, resulting in lipid peroxidation and leading to apoptosis. Taken together, these results demonstrated that KR and 7-deazaKR modulate the cellular redox environment of T98G cells, and vulnerability of these cells is dependent on their antioxidant capacity. |
| first_indexed | 2024-03-10T10:28:23Z |
| format | Article |
| id | doaj.art-83db956acc3f42ef83ec6d3716681449 |
| institution | Directory Open Access Journal |
| issn | 2076-3921 |
| language | English |
| last_indexed | 2024-03-10T10:28:23Z |
| publishDate | 2021-06-01 |
| publisher | MDPI AG |
| record_format | Article |
| series | Antioxidants |
| spelling | doaj.art-83db956acc3f42ef83ec6d37166814492023-11-21T23:50:21ZengMDPI AGAntioxidants2076-39212021-06-0110695010.3390/antiox10060950Implications of Oxidative Stress in Glioblastoma Multiforme Following Treatment with Purine DerivativesMarta Orlicka-Płocka0Agnieszka Fedoruk-Wyszomirska1Dorota Gurda-Woźna2Paweł Pawelczak3Patrycja Krawczyk4Małgorzata Giel-Pietraszuk5Grzegorz Framski6Tomasz Ostrowski7Eliza Wyszko8Institute of Bioorganic Chemistry, Polish Academy of Sciences, Noskowskiego 12/14, 61-704 Poznan, PolandInstitute of Bioorganic Chemistry, Polish Academy of Sciences, Noskowskiego 12/14, 61-704 Poznan, PolandInstitute of Bioorganic Chemistry, Polish Academy of Sciences, Noskowskiego 12/14, 61-704 Poznan, PolandInstitute of Bioorganic Chemistry, Polish Academy of Sciences, Noskowskiego 12/14, 61-704 Poznan, PolandMRC Laboratory of Molecular Biology, Francis Crick Avenue, Cambridge CB2 0QH, UKInstitute of Bioorganic Chemistry, Polish Academy of Sciences, Noskowskiego 12/14, 61-704 Poznan, PolandInstitute of Bioorganic Chemistry, Polish Academy of Sciences, Noskowskiego 12/14, 61-704 Poznan, PolandInstitute of Bioorganic Chemistry, Polish Academy of Sciences, Noskowskiego 12/14, 61-704 Poznan, PolandInstitute of Bioorganic Chemistry, Polish Academy of Sciences, Noskowskiego 12/14, 61-704 Poznan, PolandRecently, small compound-based therapies have provided new insights into the treatment of glioblastoma multiforme (GBM) by inducing oxidative impairment. Kinetin riboside (KR) and newly designed derivatives (8-azaKR, 7-deazaKR) selectively affect the molecular pathways crucial for cell growth by interfering with the redox status of cancer cells. Thus, these compounds might serve as potential alternatives in the oxidative therapy of GBM. The increased basal levels of reactive oxygen species (ROS) in GBM support the survival of cancer cells and cause drug resistance. The simplest approach to induce cell death is to achieve the redox threshold and circumvent the antioxidant defense mechanisms. Consequently, cells become more sensitive to oxidative stress (OS) caused by exogenous agents. Here, we investigated the effect of KR and its derivatives on the redox status of T98G cells in 2D and 3D cell culture. The use of spheroids of T98G cells enabled the selection of one derivative—7-deazaKR—with comparable antitumor activity to KR. Both compounds induced ROS generation and genotoxic OS, resulting in lipid peroxidation and leading to apoptosis. Taken together, these results demonstrated that KR and 7-deazaKR modulate the cellular redox environment of T98G cells, and vulnerability of these cells is dependent on their antioxidant capacity.https://www.mdpi.com/2076-3921/10/6/950purine derivativeskinetin ribosideglioblastoma multiformeoxidative therapyROSoxidative imbalance |
| spellingShingle | Marta Orlicka-Płocka Agnieszka Fedoruk-Wyszomirska Dorota Gurda-Woźna Paweł Pawelczak Patrycja Krawczyk Małgorzata Giel-Pietraszuk Grzegorz Framski Tomasz Ostrowski Eliza Wyszko Implications of Oxidative Stress in Glioblastoma Multiforme Following Treatment with Purine Derivatives Antioxidants purine derivatives kinetin riboside glioblastoma multiforme oxidative therapy ROS oxidative imbalance |
| title | Implications of Oxidative Stress in Glioblastoma Multiforme Following Treatment with Purine Derivatives |
| title_full | Implications of Oxidative Stress in Glioblastoma Multiforme Following Treatment with Purine Derivatives |
| title_fullStr | Implications of Oxidative Stress in Glioblastoma Multiforme Following Treatment with Purine Derivatives |
| title_full_unstemmed | Implications of Oxidative Stress in Glioblastoma Multiforme Following Treatment with Purine Derivatives |
| title_short | Implications of Oxidative Stress in Glioblastoma Multiforme Following Treatment with Purine Derivatives |
| title_sort | implications of oxidative stress in glioblastoma multiforme following treatment with purine derivatives |
| topic | purine derivatives kinetin riboside glioblastoma multiforme oxidative therapy ROS oxidative imbalance |
| url | https://www.mdpi.com/2076-3921/10/6/950 |
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