| Full text | |
| Author(s): |
Vital, Patrik da Silva
;
Bonatelli, Murilo
;
Dias, Marina Pereira
;
de Salis, Larissa Vedovato Vilela
;
Pinto, Mariana Tomazini
;
Baltazar, Fatima
;
Maria-Engler, Silvya Stuchi
;
Pinheiro, Celine
Total Authors: 8
|
| Document type: | Journal article |
| Source: | INTERNATIONAL JOURNAL OF MOLECULAR SCIENCES; v. 23, n. 24, p. 17-pg., 2022-12-01. |
| Abstract | |
(1) BRAF mutations are associated with high mortality and are a substantial factor in therapeutic decisions. Therapies targeting BRAF-mutated tumors, such as vemurafenib (PLX), have significantly improved the overall survival of melanoma patients. However, patient relapse and low response rates remain challenging, even with contemporary therapeutic alternatives. Highly proliferative tumors often rely on glycolysis to sustain their aggressive phenotype. 3-bromopyruvate (3BP) is a promising glycolysis inhibitor reported to mitigate resistance in tumors. This study aimed to evaluate the potential of 3BP as an antineoplastic agent for PLX-resistant melanoma treatment. (2) The effect of 3BP alone or in combination with PLX on viability, proliferation, colony formation, cell death, migration, invasion, epithelial-mesenchymal marker and metabolic protein expression, extracellular glucose and lactate, and reactive species were evaluated in two PLX-resistant melanoma cell lines. (3) 3BP treatment, which was more effective as monotherapy than combined with PLX, disturbed the metabolic and epithelial-mesenchymal profile of PLX-resistant cells, impairing their proliferation, migration, and invasion and triggering cell death. (4) 3BP monotherapy is a potent metabolic-disrupting agent against PLX-resistant melanomas, supporting the suppression of the malignant phenotype in this type of neoplasia. (AU) | |
| FAPESP's process: | 15/25351-6 - MCT1 as a target and response mediator in melanoma therapy |
| Grantee: | Céline Marques Pinheiro |
| Support Opportunities: | Research Grants - Young Investigators Grants |
| FAPESP's process: | 19/07502-8 - Investigation of the transcription factors inducing Epithelial-Mesenchymal Transition (EMT) in germ cells tumors |
| Grantee: | Mariana Tomazini Pinto |
| Support Opportunities: | Research Grants - Young Investigators Grants |
| FAPESP's process: | 19/14189-4 - Effect of 3-bromopyruvate in melanoma cells resistant to vemurafenib |
| Grantee: | Patrik da Silva Vital |
| Support Opportunities: | Scholarships in Brazil - Master |
| FAPESP's process: | 16/13021-4 - Sensitivity to 3-bromopyruvate and its relation to monocarboxylate 1 transporter (MCT-1) expression in primary melanoma cultures |
| Grantee: | Larissa Vedovato Vilela de Salis |
| Support Opportunities: | Scholarships in Brazil - Scientific Initiation |
| FAPESP's process: | 16/10821-0 - MCT1 as a target and response mediator in melanoma therapy |
| Grantee: | Murilo Queiroz de Almeida Bonatelli |
| Support Opportunities: | Scholarships in Brazil - Doctorate (Direct) |
| FAPESP's process: | 17/12620-4 - Characterization of the role of tumor metabolism in the resistance of human melanoma to Vemurafenib |
| Grantee: | Marina Pereira Dias |
| Support Opportunities: | Scholarships in Brazil - Doctorate |