“Effects of Redox Status on Immediate Hypericin-Mediated Photodynamic Therapy in Human Glioblastoma T98G Cell Line”
Glioblastoma Multiforme (GBM) is one of the most aggressive types of brain tumor. GBM can modulate glutathione (GSH) levels and regulate cellular redox state, which can explain its high resistance to chemotherapeutic agents. Photodynamic therapy (PDT) is a selective, nontoxic, and minimally invasive treatment approved for many types of cancer. PDT leads to cell death mainly by promoting the generation of reactive oxygen species (ROS). Thus, in the current study, PDT with the photosensitizer hypericin (Hyp), formulated in mixed 1,2-dipalmitoyl-<i>sn</i>-glycero-3-phosphocholine (DPPC)/biotinylated-pluronic F127 (F127-B) liposomes, in combination with the GSH synthesis inhibitor buthionine sulfoximine (BSO) were tested against T98G cell line of human glioblastoma. The mixed liposome was effective in delivering Hyp to the cells, leading to a dose relationship between Hyp and ROS levels. BSO potentiated Hyp cell uptake, decreased GSH levels regardless of Hyp concentration, and intensified ROS generation for 1.00 and 5.00 μmol L<sup>-1</sup> Hyp. Nonetheless, cell death was more pronounced in the groups not treated with BSO, indicating that reduced GSH levels are not a decisive factor in achieving the PDT effects of Hyp. In conclusion, the mixed DPPC/F127-B liposomes were effective as a delivery system for Hyp. However, the combination of BSO and Hyp was not capable of optimizing PDT against T98G cells.
Authors
- Camila Fabiano de Freitas (ORCID: https://orcid.org/0000-0002-9320-8964)
- Jurandir Fernando Comar (ORCID: https://orcid.org/0000-0002-9518-7589)
- Camila Aparecida Errerias Fernandes Cardinali (ORCID: https://orcid.org/0000-0001-9666-0430)
- Juliana Nunes de Lima Martins
- Patricia Mendonca (ORCID: https://orcid.org/0000-0002-0116-2189)
- Noboru Hioka (ORCID: https://orcid.org/0000-0003-0775-5839)
- Renato Sonchini Gonçalves (ORCID: https://orcid.org/0000-0003-2701-6101)
- Yandara Akamine Martins (ORCID: https://orcid.org/0000-0002-4513-7153)
- André Luiz Tessaro (ORCID: https://orcid.org/0000-0002-5089-9734)
- Flávia Amanda Pedroso de Morais (ORCID: https://orcid.org/0000-0003-0208-6752)
- Kellen Brunaldi (ORCID: https://orcid.org/0000-0001-9122-1455)
- Elza Kimura (ORCID: https://orcid.org/0000-0002-6466-5074)
- Maria Ida Bonini Ravanelli (ORCID: https://orcid.org/0000-0003-3249-8504)
- Wilker Caetano
Institutions
- Universidade Estadual de Maringá (BR)
- Universidade Tecnológica Federal do Paraná (BR)
- Universidade Federal de Santa Catarina (BR)
- Anesthesia Quality Institute (US)
- Departament de Salut (ES)
- Department of Physiological Sciences (RU)
Publication Details
- Journal
- ACS Omega
- Published
- 2024-12-28
- DOI
- https://doi.org/10.1021/acsomega.4c08553
- Primary Topic
- Photodynamic Therapy Research Studies
- Type
- article
- Field-Weighted Citation Impact
- 0.00
Funders
- Coordenação de Aperfeiçoamento de Pessoal de Nível Superior
- Conselho Nacional de Desenvolvimento Científico e Tecnológico
- Secretário de Ciência, Tecnologia e Ensino Superior, Governo do Estado de Parana
- Fundação Araucária
- Fundação de Amparo à Pesquisa e Inovação do Estado de Santa Catarina