Busca avançada
Ano de início
Entree


Lysicamine Reduces Protein Kinase B (AKT) Activation and Promotes Necrosis in Anaplastic Thyroid Cancer

Texto completo
Autor(es):
Mostrar menos -
Rodrigues, Mariana Teixeira ; Michelli, Ana Paula Picaro ; Caso, Gustavo Felisola ; de Oliveira, Paloma Ramos ; Rodrigues-Junior, Dorival Mendes ; Morale, Mirian Galliote ; Machado Junior, Joel ; Bortoluci, Karina Ramalho ; Tamura, Rodrigo Esaki ; da Silva, Tamiris Reissa Cipriano ; Raminelli, Cristiano ; Chau, Eric ; Godin, Biana ; Calil-Silveira, Jamile ; Rubio, Ileana G. Sanchez
Número total de Autores: 15
Tipo de documento: Artigo Científico
Fonte: PHARMACEUTICALS; v. 16, n. 12, p. 18-pg., 2023-12-01.
Resumo

Anaplastic thyroid cancer (ATC) is an aggressive form of thyroid cancer (TC), accounting for 50% of total TC-related deaths. Although therapeutic approaches against TC have improved in recent years, the survival rate remains low, and severe adverse effects are commonly reported. However, unexplored alternatives based on natural compounds, such as lysicamine, an alkaloid found in plants with established cytotoxicity against breast and liver cancers, offer promise. Therefore, this study aimed to explore the antineoplastic effects of lysicamine in papillary TC (BCPAP) and ATC (HTH83 and KTC-2) cells. Lysicamine treatment reduced cell viability, motility, colony formation, and AKT activation while increasing the percentage of necrotic cells. The absence of caspase activity confirmed apoptosis-independent cell death. Necrostatin-1 (NEC-1)-mediated necrosome inhibition reduced lysicamine-induced necrosis in KTC-2, suggesting necroptosis induction via a reactive oxygen species (ROS)-independent mechanism. Additionally, in silico analysis predicted lysicamine target proteins, particularly those related to MAPK and TGF-beta signaling. Our study demonstrated lysicamine's potential as an antineoplastic compound in ATC cells with a proposed mechanism related to inhibiting AKT activation and inducing cell death. (AU)

Processo FAPESP: 14/24549-4 - Identificação de aletrações genéticas e cromossômicas no exoma completo de pacientes com hipotireoidismo congênito por disgenesia tireoidana
Beneficiário:Ileana Gabriela Sánchez de Rubió
Modalidade de apoio: Auxílio à Pesquisa - Regular
Processo FAPESP: 23/02690-6 - Modulação da via JAK/STAT no câncer avançado de tireoide como potencial alvo terapêutico: efeito na captação de iodo, em características de células tronco tumorais
Beneficiário:Ileana Gabriela Sánchez de Rubió
Modalidade de apoio: Auxílio à Pesquisa - Regular
Processo FAPESP: 19/15619-2 - Desenvolvimento de sistema adenoviral de alta capacidade expressando genes com atividade antitumoral
Beneficiário:Rodrigo Esaki Tamura
Modalidade de apoio: Auxílio à Pesquisa - Jovens Pesquisadores