Lidocaine in oncological surgery: the role of blocking in voltage-gated sodium channels. A narrative review / Lidocaína em cirurgia oncológica: o papel do bloqueio dos canais de sódio dependentes de voltagem. Revisão narrativa

Abstract Background: The current evidence suggests that oncological surgery, which is a therapy used in the treatment of solid tumors, increases the risk of metastasis. In this regard, a wide range of tumor cells express Voltage-Gated Sodium Channels (VGSC), whose biological roles are not related to the generation of action potentials. In epithelial tumor cells, VGSC are part of cellular structures named invadopodia, involved in cell proliferation, migration, and metastasis. Recent studies showed that lidocaine could decrease cancer recurrence through its direct effects on tumor cells and immunomodulatory properties on the stress response. Objective: The aim of this narrative review is to highlight the role of VGSC in tumor cells, and to describe the potential antiproliferative effect of lidocaine during the pathogenesis of metastasis. Contents: A critical review of literature from April 2017 to April 2019 was performed. Articles found on PubMed (2000-2019) were considered. A free text and MeSH-lidocaine; voltage-gated sodium channels; tumor cells; invadopodia; surgical stress; cell proliferation; metastasis; cancer recurrence - for articles in English, Spanish and Portuguese language - was used. A total of 62 were selected. Conclusion: In animal studies, lidocaine acts by blocking VGSC and other receptors, decreasing migration, invasion, and metastasis. These studies need to be replicated in humans in the context of oncological surgery.

Resumo Justificativa: As evidências atuais sugerem que a cirurgia oncológica, usada no tratamento de tumores sólidos, aumenta o risco de metástase. Nesse sentido, uma ampla gama de células tumorais expressa Canais de Sódio Dependentes de Voltagem (CSDV), cujos papéis biológicos não estão relacionados à produção de potencial de ação. Nas células epiteliais tumorais, o CSDV é parte integrante de estruturas celulares denominadas invadópodes, que participam da proliferação, migração e metástase celular. Estudos recentes mostraram que a lidocaína pode diminuir a recorrência do câncer através de efeitos diretos nas células tumorais e de propriedades imunomoduladoras na resposta ao estresse. Objetivo: O objetivo desta revisão narrativa é analisar o papel do CSDV nas células tumorais e descrever o possível efeito antiproliferativo da lidocaína na patogênese das metástases. Conteúdo: Foi realizada uma revisão crítica da literatura de Abril de 2017 a Abril de 2019. Os artigos encontrados no PubMed (2000 − 2019) foram analisados. Pesquisamos textos de linguagem livre e descritores MeSH-lidocaína; canais de sódio dependentes de voltagem; células tumorais; invadópodes; estresse cirúrgico; proliferação celular; metástase; recorrência do câncer − em artigos publicados em inglês, espanhol e português. Foram selecionadas 62 publicações. Conclusão: Em estudos empregando animais, a lidocaína atua bloqueando o CSDV e outros receptores, diminuindo a migração, invasão e metástase. Esses estudos precisam ser replicados em humanos submetidos a cirurgia oncológica.

Is there a role for voltage-gated Na+ channels in the aggressiveness of breast cancer?

Breast cancer is the most common cancer among women and its metastatic potential is responsible for numerous deaths. Thus, the need to find new targets for improving treatment, and even finding the cure, becomes increasingly greater. Ion channels are known to participate in several physiological functions, such as muscle contraction, cell volume regulation, immune response and cell proliferation. In breast cancer, different types of ion channels have been associated with tumorigenesis. Recently, voltage-gated Na+ channels (VGSC) have been implicated in the processes that lead to increased tumor aggressiveness. To explain this relationship, different theories, associated with pH changes, gene expression and intracellular Ca2+, have been proposed in an attempt to better understand the role of these ion channels in breast cancer. However, these theories are having difficulty being accepted because most of the findings are contrary to the present scientific knowledge. Several studies have shown that VGSC are related to different types of cancer, making them a promising pharmacological target against this debilitating disease. Molecular biology and cell electrophysiology have been used to look for new forms of treatment aiming to reduce aggressiveness and the disease progress.

Physiological and biochemical characterization of egg extract of black widow spiders to uncover molecular basis of egg toxicity

BACKGROUND: Black widow spider (L. tredecimguttatus) has toxic components not only in the venomous glands, but also in other parts of the body and its eggs. It is biologically important to investigate the molecular basis of the egg toxicity. RESULTS: In the present work, an aqueous extract was prepared from the eggs of the spider and characterized using multiple physiological and biochemical strategies. Gel electrophoresis and mass spectrometry demonstrated that the eggs are rich in high-molecular-mass proteins and the peptides below 5 kDa. The lyophilized extract of the eggs had a protein content of 34.22% and was shown to have a strong toxicity towards mammals and insects. When applied at a concentration of 0.25 mg/mL, the extract could completely block the neuromuscular transmission in mouse isolated phrenic nerve-hemidiaphragm preparations within 12.0 ± 1.5 min. Using whole-cell patch-clamp technique, the egg extract was demonstrated to be able to inhibit the voltage-activated Na+, K+and Ca2+ currents in rat DRG neurons. In addition, the extract displayed activities of multiple hydrolases. Finally, the molecular basis of the egg toxicity was discussed. CONCLUSIONS: The eggs of black widow spiders are rich in proteinous compounds particularly the high-molecular-mass proteins with different types of biological activity The neurotoxic and other active compounds in the eggs are believed to play important roles in the eggs' toxic actions.