Proteomic analysis reveals stage-specific reprogramed metabolism for the primary breast cancer cell lines MGSO-3 and MACL-1.

Breast cancer is the most prevalent cancer in women worldwide. Its molecular subtypes are based on the presence/absence of estrogen receptor (ER), progesterone receptor (PR), and human epidermal growth factor receptor 2 (HER2). MACL-1 and MGSO-3 are cell lines derived from primary tumor sites of patients diagnosed with luminal A subtype carcinoma (ER+/PR+/HER2-) and ductal carcinoma in situ (ER-/PR-/HER2+), respectively. However, these cell lines lost the expression of these markers over cell culturing, and both have triple-negative phenotypes (ER-/PR-/HER2-), which has the poorest prognosis. Here, we sought to study the proteome signature of MGSO-3 and MACL-1, comparing them with the epithelial cell line MCF-10A and the well-established metastatic-derived breast cancer cell line MDA-MB-231. Our results showed that proteins associated with the tricarboxylic acid cycle (TCA) and oxidative phosphorylation (OXPHOS) were upregulated in MGSO-3 and MACL-1 cells. These cell lines also showed upregulation of pro-apoptotic proteins when compared with MDA-MB-231. The molecular differences highlighted in this study may clarify the molecular basis behind cancer cells functioning and may reveal novel signatures across the breast cancer cell models.

Breast cancer: Is grief a risk factor?

Cancer is characterized by the disordered growth of cells that have high capacity of invasion to the tissues and organs. One of the types of tumour that has national incidence and high mortality is breast cancer. Studies show that in addition to hereditary factors, lifestyle and environmental factors, there are factors related to emotional distress (mourning), which interfere with the development of breast cancer. Thus, it is necessary to investigate if the experience of mourning can trigger the appearance of the tumour. For this, an integrative review was performed to verify the existence of the relationship between mourning and development of breast cancer, which presented contradictory results. Methodological errors and lack of access to important information, such as alcohol and tobacco use, were pointed out as the main causes of the contradiction found. A possible mechanism involving cortisol release has been proposed, but more research is needed to make it clear whether the association between mourning and breast cancer really exists, and by what path.

N-salicyloyltryptamine, a new anticonvulsant drug, acts on voltage-dependent Na+, Ca2+, and K+ ion channels.

1. The aim of this work was to study the effects of N-salicyloyltryptamine (STP), a novel anticonvulsant agent, on voltage-gated ion channels in GH3 cells. 2. In this study, we show that STP at 17 microM inhibited up to 59.2+/-10.4% of the Ito and 73.1+/-8.56% of the IKD K+ currents in GH3 cells. Moreover, the inhibitory activity of the drug STP on K+ currents was dose-dependent (IC50=34.6+/-8.14 microM for Ito) and partially reversible after washing off. 3. Repeated stimulation at 1 Hz (STP at 17 microM) led to the total disappearance of Ito current, and an enhancement of IKD. 4. In the cell-attached configuration, application of STP to the bath increased the open probability of large-conductance Ca2+-activated K+ channels. 5. STP at 17 microM inhibited the L-type Ca2+ current by 54.9+/-7.50% without any significant changes in the voltage dependence. 6. STP at 170 microM inhibited the TTX-sensitive Na+ current by 22.1+/-2.41%. At a lower concentration (17 microM), no effect on INa was observed. 7. The pharmacological profile described here might contribute to the neuroprotective effect exerted by this compound in experimental 'in vivo' models.

Câncer de mama: Reprogramação do metabolismo tumoral / Breast Cancer: tumoral metabolism reprogramming

O câncer de mama é a neoplasia de maior incidência em mulheres de todo o mundo, cuja mortalidade se deve principalmente ao desenvolvimento de metástases (condição patológica em que as células tumorais conseguem atravessar a matriz extracelular e se estabelecer em outros tecidos). Devido à importância epidemiológica dessa doença, estudos têm sido realizados em busca de uma melhor compreensão dos processos que atuam na carcinogênese e/ou tumorigênese e que, consequentemente, levam ao desenvolvimento de novas formas de diagnóstico e tratamento que sejam cada vez mais efetivos. Para manter a alta taxa de proliferação e desenvolver um perfil agressivo, características que são observadas em células tumorais, diversas alterações no metabolismo celular se tornam necessárias. O metabolismo tumoral começou a ser descrito por Otto Warburg em 1920, onde afirma que células cancerosas metabolizam glicose de forma diferente das células normais através da glicólise aeróbica. Dados recentes mostram que as alterações também ocorrem no metabolismo lipídico, apontando para uma reprogramação celular. A possibilidade de novos alvos farmacológicos inseriu o metabolismo como alvo das pesquisas recentes. Entretanto, e apesar do avanço, 90 anos depois da descoberta feita por Warburg, os estudos ainda não conseguiram esclarecer por completo como o metabolismo tumoral funciona, demonstrando assim a necessidade de mais pesquisas. Tendo em vista este cenário, essa revisão tem como objetivo documentar e discutir os principais resultados obtidos até o momento, como apontar e sugerir áreas de investigação. (AU)

Breast cancer is the most prevalent neoplasm in women worldwide, whose mortality is mainly due to the development of metastasis (pathological condition in which cancer cells can cross the extracellular matrix and settle in other tissues). Due to the epidemiological importance of this disease, studies have been carried out in order to better understand the processes involved in carcinogenesis and/or tumorigenesis and, consequently, allow the development of new forms of diagnosis and treatment that are increasingly effective. To maintain the high proliferation rate and develop an aggressive profile, features that are observed in tumor cells, several changes in cellular metabolism become necessary. Tumor metabolism began to be described by Otto Warburg in 1920, where he states that cancer cells metabolize glucose differently from normal cells through aerobic glycolysis. Recent data show that changes also occur in lipid metabolism, pointing to cellular reprogramming. The possibility of new pharmacological targets, inserted the metabolism as a target of recent research. However, despite the breakthrough, 90 years after Warburg discovery, studies have not yet been able to fully clarify how tumor metabolism works, demonstrating the need for more research. In view of this scenario, this review aims to document the main results obtained so far and to discuss those aspects that are not yet well understood. (AU)

Breast cancer: Is grief a risk factor?

SUMMARY Cancer is characterized by the disordered growth of cells that have high capacity of invasion to the tissues and organs. One of the types of tumour that has national incidence and high mortality is breast cancer. Studies show that in addition to hereditary factors, lifestyle and environmental factors, there are factors related to emotional distress (mourning), which interfere with the development of breast cancer. Thus, it is necessary to investigate if the experience of mourning can trigger the appearance of the tumour. For this, an integrative review was performed to verify the existence of the relationship between mourning and development of breast cancer, which presented contradictory results. Methodological errors and lack of access to important information, such as alcohol and tobacco use, were pointed out as the main causes of the contradiction found. A possible mechanism involving cortisol release has been proposed, but more research is needed to make it clear whether the association between mourning and breast cancer really exists, and by what path.

RESUMO: O câncer é caracterizado pelo crescimento desordenado das células que possuem alta capacidade de invasão aos tecidos e órgãos. Um dos tipos de tumour que possui incidência nacional e alta mortalidade é o câncer de mama. Estudos mostram que, além dos fatores hereditários, ambientais e dos hábitos de vida, existem fatores relacionados a um trauma emocional (luto) que interferem no desenvolvimento do câncer de mama. Dessa forma, é necessário investigar se a vivência do luto pode desencadear o aparecimento do tumour. Para isso, realizou-se uma revisão integrativa para verificar a existência da relação entre o luto e o desenvolvimento do câncer de mama, que apresentou resultados contraditórios. Os erros metodológicos e a falta de acesso a informações importantes, como uso de álcool e fumo, foram apontadas como as principais causas da contradição encontrada. Um possível mecanismo envolvendo liberação de cortisol tem sido proposto, mas são necessárias mais investigações para que fique claro se a associação entre luto e câncer de mama realmente existe, e por qual mecanismo ocorre.