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Acetylation of cedrelone increases its cytotoxic activity and reverts the malignant phenotype of breast cancer cells in 3D culture

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Becceneri, Amanda Blanque [1] ; Fuzer, Angelina Maria [1] ; Popolin, Cecilia Patricia [1] ; Cazal, Cristiane de Melo [2] ; Domingues, Vanessa de Cassia [3] ; Fernandes, Joao Batista [3] ; Vieira, Paulo Cezar [4] ; Cominetti, Marcia Regina [1]
Número total de Autores: 8
Afiliação do(s) autor(es):
[1] Univ Fed Sao Carlos, Dept Gerontol, Rod Washington Luis, Km 235, Sao Carlos, SP - Brazil
[2] Fed Inst Goiano, Rodovia GO 060 Km 0 1, Ipora, Go - Brazil
[3] Univ Fed Sao Carlos, Dept Chem, Rod Washington Luis, Km 235, Sao Carlos, SP - Brazil
[4] Univ Sao Paulo, Sch Pharmaceut Sci Ribeirao Preto, Av Cafe, Ribeirao Preto, SP - Brazil
Número total de Afiliações: 4
Tipo de documento: Artigo Científico
Fonte: Chemico-Biological Interactions; v. 316, JAN 25 2020.
Citações Web of Science: 0

Cedrelone is a limonoid isolated from the plant Trichilia catigua (Meliaceae). Previous studies have demonstrated that cedrelone (1) has several damaging effects on triple negative breast tumor (TNBC) cell line MDA-MB-231. In this work we investigated two new derivatives of cedrelone, the acetate (1a) and the mesylate (1b), to examine whether their effects are improved in comparison to the lead molecule. Cedrelone acetate (1a) was the most cytotoxic compound on TNBC cells and was chosen for additional analyses in traditional two-dimensional (2D) monolayer cultures and three-dimensional (3D) assays. In 2D, 1a induced cell cycle arrest, apoptosis and inhibited essential steps of the metastasis process of the MDA-MB-231 cells, in vitro. Moreover, 1a was able to revert the malignant phenotype of the T4-2 cells in 3D. These effects were concomitant with the downregulation of EGFR, beta 1-integrin and phospho-Akt, which could have resulted in a decrease of NF kappa B levels and MMP9 activity. These results suggest that 1a could be used as an important model for the design of a new drug to be applied in cancer treatment and be further studied in vivo for its antitumor and antimetastatic effects. (AU)

Processo FAPESP: 17/01287-2 - Triagem dè compostos candidatos a novos medicamentos antitumorais pôr cultura celular tridimensional
Beneficiário:Angelina Maria Fuzer
Linha de fomento: Bolsas no Brasil - Pós-Doutorado
Processo FAPESP: 12/25299-6 - Estudos integrados para o controle de formigas cortadeiras
Beneficiário:João Batista Fernandes
Linha de fomento: Auxílio à Pesquisa - Temático
Processo FAPESP: 14/25121-8 - Atividade antitumoral e potencial mutagênico dè novos complexos dè rutênio
Beneficiário:Amanda Blanque Becceneri
Linha de fomento: Bolsas no Brasil - Doutorado