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Ovarian cancer (OC) is the most lethal gynecologic malignancy, and melatonin has shown various antitumor properties. Herein, we investigated the influence of melatonin therapy on energy metabolism and mitochondrial integrity in SKOV-3 cells and tested whether its effects depended on MT1 receptor activation. SKOV-3 cells were exposed to different melatonin concentrations, and experimental groups were divided as to the presence of MT1 receptors (melatonin groups) or receptor absence by RNAi silencing (siRNA MT1+melatonin). Intracellular melatonin levels increased after treatment with melatonin independent of the MT1. The mitochondrial membrane potential of SKOV-3 cells decreased in the group treated with the highest melatonin concentration. Melatonin reduced cellular glucose consumption, while MT1 knockdown increased its consumption. Interconversion of lactate to pyruvate increased after treatment with melatonin and was remarkable in siRNA MT1 groups. Moreover, lactate dehydrogenase activity decreased with melatonin and increased after MT1 silencing at all concentrations. The UCSC XenaBrowser tool showed a positive correlation between the human ASMTL gene and the ATP synthase genes, succinate dehydrogenase gene (SDHD), and pyruvate dehydrogenase genes (PDHA and PDHB). We conclude that melatonin changes the glycolytic phenotype and mitochondrial integrity of SKOV-3 cells independent of the MT1 receptor, thus decreasing the survival advantage of OC cells.

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Ovarian cancer (OC) has a high mortality rate. Although most patients respond to the conventional chemotherapy [e.g., paclitaxel (PTX)], some also develop drug resistance to make the treatment less effective. Since melatonin exhibits antioxidant, antitumor, and immunomodulatory functions in a variety of solid tumors, in this study the effects of a combination of PTX and melatonin on SKOV-3 human ovarian carcinoma cells were investigated and the focus was given to the Toll-like receptor (TLR)-mediated inflammatory pathway and cell signaling-related molecules. Flow cytometry showed that this combination significantly boosted the apoptosis/necrosis responses of the cancer cells. Cell migration was attenuated by melatonin alone, and the combination led to a reduced number of migrating and invasive cells. Melatonin alone and its combination also reduced the levels of TLR4, MyD88, TRIF, and PD-L1, but not TLR2. In addition, the combination significantly lowered the levels of NF-kB p65, PI3K, p-AKT, p38, ERK 1/2, JNK, CREB, p70s6K, and STAT5. The results suggested that this combination was effective in reducing the viability and the invasive capacity of SKOV-3 cells while increasing their apoptosis and necrosis rates. The potential mechanism of this combination is to attenuate the downstream molecules of the TLR4-mediated inflammatory pathway and cell signaling-related proteins in the cancer cells. Thus, melatonin improved the chemosensitivity of the cancer cells to PTX, serving as an effective adjuvant therapy against OC.

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A música expressa ideias individuais ou da sociedade, presentes em determinadas épocas da História, servindo como um importante instrumento pedagógico de entendimento interdisciplinar dos conteúdos, em todas as etapas da educação. Além disso, a música exerce um importante papel na plasticidade cerebral, que é a capacidade do cérebro de modificar sua organização estrutural e funcionamento. O objetivo do presente trabalho é relatar a exposição do estande Musicalizando, no evento Conhecendo o Cérebro, realizado pelo Grupo de Estudos em Neurociência da Universidade Estadual do Norte do Paraná (UENP), uma ação extensionista que utiliza a divulgação científica para tradução e comunicação do conhecimento científico para a sociedade. Tal estande foi dividido em dois momentos: um primeiro teórico, no qual havia uma explicação sobre os efeitos da música no cérebro e também relatava-se a importância da música como veículo de expressão cultural e protesto. Posteriormente, as monitoras mostravam aos visitantes os instrumentos musicais construídos por elas mesmas, ressaltando a ideia de que para fazer música não é necessário possuir instrumentos caros. Mais de 570 pessoas foram alcançadas durante os dois dias de evento. Os visitantes marcaram em um papel qual emoji representava a sua opinião (detestei; não gostei; indiferente; gostei; gostei muito) sobre o estande; 95,4% dos visitantes assinalaram a opção “gostei muito” e 4,6% assinalaram “gostei”. Eventos que proporcionam a divulgação científica de forma mais interativa podem incentivar os visitantes a conhecerem mais sobre o tema proposto. Ademais, ações que envolvem música têm a possibilidade de estimular a integração social, a cooperação e o trabalho em grupo. Palavras-chave: Extensão Universitária; Música; Educação; Neurociências   "Musicalizing" Intervention: Musical Experimentation in an Extension Action Abstract: Music expresses individual or societal ideals at a particular moment of History, serving as an essential pedagogical instrument it offers an interdisciplinary understanding of contents in all stages of education. Also, music plays an important role in brain plasticity, which is the brain's ability to modify its structural organization and functioning. The objective of the present work is to report the stand "Making music" at the "Knowing the Brain" event held by the Neuroscience Studies Group of Universidade Estadual do Norte do Paraná, an extensionist action that uses scientific dissemination for translation and communication of scientific knowledge to society. This stand was divided into two moments. First, a theoretical moment, in which there was an explanation of the effects of music in the brain, and the importance of music as a vehicle of cultural expression and protest. Subsequently, the monitors showed the visitors the musical instruments they built, emphasizing the idea that to make music, it is not necessary to have expensive instruments. More than 570 visitors were reached during the two-day event. The visitors marked in a paper in which emoji represented their opinion on the booth (hated, disliked, indifferent, liked, and loved). 95.4% of the visitants indicated the option "loved" and 4.6% indicated "liked". Events that provide scientific dissemination, interactively, can encourage the visitors to know more about the proposed theme. In addition, actions involving music have the possibility of stimulating social integration, cooperation, and group work. Keywords: University Extension; Music; Education; Neuroscience   Intervención "Musicalización": Experimentación Musical en una acción de extensión Resumen: La música expresa ideas individuales o de la sociedad, presentes en ciertos momentos de la Historia, sirviendo como un importante instrumento pedagógico para la comprensión interdisciplinaria de los contenidos en todas las etapas de la educación. Además, la música juega un papel importante en la plasticidad del cerebro, que es la capacidad del cerebro para modificar su organización y funcionamiento estructural. El objetivo de este trabajo es informar sobre la exposición del stand “Musicalizando” en el evento “Conociendo el cerebro” realizado por el Grupo de Estudos em Neurociência da Universidade Estadual do Norte do Paraná (UENP), una acción de extensión que utiliza la difusión científica para la traducción y comunicación del conocimiento científico a la sociedad. Esta cabina se dividió en dos momentos: un teórico, en el que hubo una explicación de los efectos de la música en el cerebro, que también informó sobre la importancia de la música como vehículo para la expresión cultural y la protesta. Posteriormente, los monitores mostraron a los visitantes los instrumentos musicales construidos por ellos, enfatizando la idea de que hacer música no requiere instrumentos caros. Más de 570 visitantes fueron alcanzados durante los dos días del evento. Los visitantes marcaron en un papel que los emoji representaban la opinión (odiados, disgustados, indiferentes, les gustaba, les gustaba mucho) sobre el stand. El 95,4% de los visitantes marcaron "me gusta mucho" y el 4,6% marcaron "me gusta". Los eventos que brindan difusión científica de una manera más interactiva pueden alentar a los visitantes a conocer más sobre el tema propuesto. Además, las acciones relacionadas con la música tienen la posibilidad de estimular la integración social, la cooperación y el trabajo grupal. Palabras-clave: Extensión universitaria; Música; Educación; Neurociencias