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https://hdl.handle.net/10316/113819
Título: | Counteracting Colon Cancer by Inhibiting Mitochondrial Respiration and Glycolysis with a Selective PKCδ Activator | Autor: | Bessa, Cláudia Loureiro, Joana B. Barros, Matilde Isca, Vera M. S. Sardão, Vilma A. Oliveira, Paulo J. Bernardino, Raquel L. Herman-de-Sousa, Carina Costa, Maria Adelina Correia-de-Sá, Paulo Alves, Marco G. Rijo, Patrícia Saraiva, Lucília |
Palavras-chave: | Roy-Bz; PKCδ; anticancer agent; OXPHOS; glycolysis | Data: | 2023 | Editora: | MDPI | Projeto: | This research was funded by financial support from national funds (FCT/MCTES, Fundação para a Ciência e Tecnologia and Ministério da Ciência, Tecnologia e Ensino Superior) through LAQV/REQUIMTE (UID/QUI/50006/2020), CBIOS (UIDB/04567/2020, UIDP/04567/2020), UMIB (UIDB/00215/2020, UIDP/00215/2020, LA/P/0064/2020), ITR (LA/P/0064/2020). Vera M. S. Isca (SFRH/BD/137671/2018); Marco G. Alves (2021.03439.CEECIND). Also, this work was financed by the European Regional Development Fund (ERDF), through the Centro 2020 Regional Operational Programme under project CENTRO-01-0246-FEDER-000010 (Multidisciplinary Institute of Ageing, Coimbra) through the COMPETE 2020—Operational Programme for Competitiveness and Internationalisation and Portuguese national funds via FCT—Fundação para a Ciência e a Tecnologia, under project[s] UIDB/04033/2020 and UIDB/04539/2020, UIDP/04539/2020 and LA/P/0058/2020. | Título da revista, periódico, livro ou evento: | International Journal of Molecular Sciences | Volume: | 24 | Número: | 6 | Resumo: | Metabolic reprogramming is a central hub in tumor development and progression. Therefore, several efforts have been developed to find improved therapeutic approaches targeting cancer cell metabolism. Recently, we identified the 7a-acetoxy-6b-benzoyloxy-12-O-benzoylroyleanone (Roy- Bz) as a PKC -selective activator with potent anti-proliferative activity in colon cancer by stimulating a PKC -dependent mitochondrial apoptotic pathway. Herein, we investigated whether the antitumor activity of Roy-Bz, in colon cancer, could be related to glucose metabolism interference. The results showed that Roy-Bz decreased the mitochondrial respiration in human colon HCT116 cancer cells, by reducing electron transfer chain complexes I/III. Consistently, this effect was associated with downregulation of the mitochondrial markers cytochrome c oxidase subunit 4 (COX4), voltage-dependent anion channel (VDAC) and mitochondrial import receptor subunit TOM20 homolog (TOM20), and upregulation of synthesis of cytochrome c oxidase 2 (SCO2). Roy-Bz also dropped glycolysis, decreasing the expression of critical glycolytic markers directly implicated in glucose metabolism such as glucose transporter 1 (GLUT1), hexokinase 2 (HK2) and monocarboxylate transporter 4 (MCT4), and increasing TP53-induced glycolysis and apoptosis regulator (TIGAR) protein levels. These results were further corroborated in tumor xenografts of colon cancer. Altogether, using a PKC -selective activator, this work evidenced a potential dual role of PKC in tumor cell metabolism, resulting from the inhibition of both mitochondrial respiration and glycolysis. Additionally, it reinforces the antitumor therapeutic potential of Roy-Bz in colon cancer by targeting glucose metabolism. | URI: | https://hdl.handle.net/10316/113819 | ISSN: | 1422-0067 | DOI: | 10.3390/ijms24065710 | Direitos: | openAccess |
Aparece nas coleções: | I&D CIBB - Artigos em Revistas Internacionais I&D CNC - Artigos em Revistas Internacionais |
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Ficheiro | Descrição | Tamanho | Formato | |
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Counteracting-Colon-Cancer-by-Inhibiting-Mitochondrial-Respiration-and-Glycolysis-with-a-Selective-PKC-ActivatorInternational-Journal-of-Molecular-Sciences.pdf | 2.9 MB | Adobe PDF | Ver/Abrir |
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