Background The Notch signaling pathway and its modulators are directly related to growth, verticalization and metastasis in melanoma, being a possible therapeutic target for the treatment of this type of cancer. There are several methods of molecular biology to identify and quantify Notch receptors and it is essential to study them for understanding the different results, advantages and disadvantages of each. Main body The present study brings a bibliographic review on the molecular biology methods used in the identification and quantification of these molecules, aiming to facilitate research involving Notch receptors in human melanoma. We identified as main methods of molecular biology Western Blotting, Quantitative real-time polymerase chain reaction and DNA microarrays. A brief description of these methodologies is made and the advantages and disadvantages of each are discussed. Results concerning the function of this pathway are also discussed. Short conclusion It is known that the activation of Notch receptors is tumorigenic in most cases, however, depending on the microenvironment, it can provide tumor suppression. The adequate choice and use of the methodology for identification and quantification of Notch receptors is essential for the progress of knowledge of this important signaling pathway, which, certainly, will allow advances in the treatment of cutaneous melanoma.
Melanoma is the skin cancer with higher mortality and more and more cases are arising every year. Overexpression of Notch signaling pathway elements have already been found in primary and metastatic melanoma lineages, and directly correlated to melanoma’s development, growth, angiogenesis, metastasis, and resistance to treatment. Thus, target therapy against Notch in melanoma presents a high potential for the treatment of this type of cancer. In this review we aim to perform a narrative review on melanoma’s possible treatments targeting the Notch pathway. We searched literature about Notch signaling pathway inhibitors in human cutaneous melanoma published between 2000 and 2020 using MEDLINE (via PubMed), LILACS (via Biblioteca Virtual em Saúde) and Cochrane Library databases. The selected articles were analyzed, summarized, tabulated, and used to produce the present narrative review. The 24 selected articles, as well as articles referenced in them, presented as targeting therapy against Notch, γ-secretase inhibitors (GSIs), primarily, but also gliotoxin, honokiol, phospholipase A2, andrographolide and monoclonal antibodies, that, however, were not directly studied in melanoma. Another therapy that indirectly interfered in the Notch signaling pathway and was found in these articles were G9a inhibitors. Analyzing the collected data, it was possible to conclude that GSIs, more extensively studied, are probably not the best option for melanoma’s treatment, exceeding specific scenarios or through their concomitant use with other pathways inhibitors. The use of the other compounds, on the other hand, has greater potential, however, more studies are needed to prove its effectiveness and viability for the treatment of human cutaneous melanoma.
Introdução: O câncer de pele é o mais frequente no Brasil e representa 30% de todos os tumores malignos registrados no país. Alguns compostos bioativos presentes nos alimentos como carotenóides (betacaroteno, licopeno), probióticos e ômega-3, extrato de própolis, podem auxiliar na proteção da pele contra os danos causados por raios ultravioleta. Material e método: Para atingir o objetivo foi realizada uma revisão bibliográfica para avaliar a ação fotoprotetora dos compostos bioativos, nas principais bases de dados em saúde Pubmed, Lilacs e Scielo, com palavras-chave: neoplasias cutâneas, dieta, fotoproteção, nos idiomas português e inglês, considerando o período de 2008 a 2019. Resultado: O uso de betacaroteno na fotoproteção mostrou-se eficaz, com suplementação diária entre 15 mg e 180 mg e protegeu a pele contra queimaduras solares. Extrato de tomate contendo licopeno conferiu proteção contra danos agudos à pele causados pela exposição solar à longo prazo. A suplementação de licopeno e luteína protegeu a pele contra danos à pele causados pela radiação solar. A ingestão diária da bebida polifenol chá verde por 12 semanas apresentou efeito fotoprotetor. Observou-se que substâncias não tóxicas consumidas na dieta como polifenóis em frutas, vegetais, vinho, chá e cafeína, ou disponíveis na forma oral de suplementos, podem aumentar a produção de ATP e inibir a produção de ROS ou diminui a produção de PGE2, causando redução dos danos induzidos pela luz solar em humanos e protegendo a pele por vários mecanismos potenciais. Extrato de própolis tem sido utilizado no preparo de alimentos e bebidas com a finalidade de melhorar ou prevenir o câncer, e a fruta romã pode exercer ação antiinflamatória, antiproliferativa e ter efeitos anti-tumorigênicos. Conclusão: Conforme os artigos estudados, o consumo dos compostos bioativos carotenoides como betacaroteno e licopeno, flavonóides, polifenóis, cafeína, ácidos graxos poli-insaturados ômega-3, vitamina E e minerais como o selênio, são estratégias eficientes na proteção da pele contra a radiação solar, diminuindo o risco do câncer de pele. Entretanto, mais estudos clínicos randomizados precisam ser realizados para confirmar seus efeitos e estabelecer doses adequadas para efeito fotoprotetor.
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