(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.

(1) Background: Malignant gliomas are aggressive tumors characterized by fast cellular growth and highly invasive properties. Despite all biological and clinical advances in therapy, the standard treatment remains essentially palliative. Therefore, searching for alternative therapies that minimize adverse symptoms and improve glioblastoma patients’ outcomes is imperative. Natural products represent an essential source in the discovery of such new drugs. Plants from the cerrado biome have been receiving increased attention due to the presence of secondary metabolites with significant therapeutic potential. (2) Aim: This study provides data on the cytotoxic potential of 13 leaf extracts obtained from plants of 5 families (Anacardiaceae, Annonaceae, Fabaceae, Melastomataceae e Siparunaceae) found in the Brazilian cerrado biome on a panel of 5 glioma cell lines and one normal astrocyte. (3) Methods: The effect of crude extracts on cell viability was evaluated by MTS assay. Mass spectrometry (ESI FT-ICR MS) was performed to identify the secondary metabolites classes presented in the crude extracts and partitions. (4) Results: Our results revealed the cytotoxic potential of Melastomataceae species Miconia cuspidata, Miconia albicans, and Miconia chamissois. Additionally, comparing the four partitions obtained from M. chamissois crude extract indicates that the chloroform partition had the greatest cytotoxic activity against the glioma cell lines. The partitions also showed a mean IC50 close to chemotherapy, temozolomide; nevertheless, lower toxicity against normal astrocytes. Analysis of secondary metabolites classes presented in these crude extracts and partitions indicates the presence of phenolic compounds. (5) Conclusion: These findings highlight M. chamissois chloroform partition as a promising component and may guide the search for the development of additional new anticancer therapies.

Introdução: O câncer de pulmão de pequenas células (CPPC) afeta, em média,200.000 pessoas no mundo, anualmente, correspondendo a 15-20% de todos os cânceres de pulmão. Em geral, tumores sólidos reprogramam seu metabolismo aumentando a dependência na glicólise, mesmo em condições aeróbias (efeito Warburg), sendo uma das características fundamentais do câncer. Objetivo: Avaliar a expressão de proteínas relacionadas ao metabolismo glicolítico em amostras de CPPC preservadas em meio líquido. Material e Métodos: Foram incluídos 45 pacientes diagnosticados com CPPC, submetidos a lavagem brônquica em ambos os pulmões, cujas amostras (normal e tumoral) foram armazenadas em meio líquido (BD SurePathÒ). A expressão das proteínas MCT1, MCT4, GLUT1 e CA9 foi avaliada por imunocitoquímica (ICQ) em cell blocks, seguida de avaliação por patologista e, por fim, análise estatística. Resultados: Foi observada uma perda importante de amostras durante a construção dos cell blocks, na ICQ e por falta de representatividade celular. Das remanescentes, 1 amostra tumoral (12,5%) foi positiva para MCT1, 2 amostras normais (9,1%) e 2 tumorais (14,3%) foram positivas para MCT4, 1 amostra normal (4,2%) e 3 amostras tumorais (21,4%) foram positivas para GLUT1 (p=0,043) e 1 amostra tumoral (7,1%) foi positiva para CA9. Devido ao reduzido número de casos positivos, não foi possível verificar possíveis associações com os dados clínicos e patológicos dos pacientes. Conclusão: A expressão de MCT1, MCT4 e CA9 foi observada em poucas amostras, não sendo observada diferença entre amostras normais e tumorais. Para GLUT1, observou-se um aumento significativo da expressão citoplasmática nas amostras tumorais, comparando às normais.