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SSi6 promotes cell death by apoptosis through cell cycle arrest and inhibits migration and invasion of MDA-MB-231 human breast cancer cells

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Luna-Dulcey, Liany [1] ; da Silva, James A. [2] ; Cominetti, Marcia R. [1]
Número total de Autores: 3
Afiliação do(s) autor(es):
[1] Univ Fed Sao Carlos, Dept Gerontol, Lab Biol Aging LABEN, Rod Washington Luis, Km 235, BR-13565905 Sao Carlos, SP - Brazil
[2] Univ Fed Sergipe, Dept Pharm, Sao Jose, SE - Brazil
Número total de Afiliações: 2
Tipo de documento: Artigo Científico
Fonte: ANTI-CANCER DRUGS; v. 31, n. 1, p. 35-43, JAN 2020.
Citações Web of Science: 0

Triple-negative breast cancer subtype is the most aggressive type of breast cancer due to the lack of specific therapeutic targets, having limited treatment options, low survival prognosis and high recurrence rates. In this work, we describe the effects of a semisynthetic derivative of {[}6]-gingerol (6G) called SSi6, produced by the addition of a 2,4-dinitrophenylhydrazine reagent on several aspects of triple-negative breast cancer biology. Human breast cancer cell lines MDA-MB-231 and MCF-10A were used in the experiments. MTT assays were used to detect cell viability. Cell cycle and apoptosis assay were analyzed using flow cytometer Accuri C6 and analysis of proteins as retinoblastoma Rb and kinases Cdk4/6 were analyzed by western blotting. SSi6 induced cytotoxic effects on triple-negative breast cancer cells, with higher selectivity when compared to the non-tumor MCF-10A cells. In addition, SSi6 inhibited migration and invasion of triple-negative breast cancer cells and was able to arrest cell cycle at the G1-phase, mainly by decreasing Cdk4/6-Rb axis levels. Therefore, SSi6 provoked the induction of apoptosis in triple-negative breast cancer cells. SSi6 was more efficient in producing these effects, compared to the original 6G natural product. This study may contribute to a better understanding of the effects of natural and semisynthetic products on the in-vitro metastatic processes in the MDA-MB-231 triple-negative breast cancer cell line. Additional, it can be useful to understand the effects of chemical modifications on already effective natural compounds aiming at the improvement of their bioactive properties, such as in the increase of the cytotoxic selectivity against tumor cells, compared to non-tumor ones. Copyright (C) 2019 Wolters Kluwer Health, Inc. All rights reserved. (AU)

Processo FAPESP: 13/07600-3 - CIBFar - Centro de Inovação em Biodiversidade e Fármacos
Beneficiário:Glaucius Oliva
Linha de fomento: Auxílio à Pesquisa - Centros de Pesquisa, Inovação e Difusão - CEPIDs
Processo FAPESP: 18/05594-0 - Avaliação do mecanismo de ação do SSi6 na indução de autofagia e apoptose em células tumorais triplo negativas: estudos in vitro e in vivo
Beneficiário:Liany Johanna Luna Dulcey
Linha de fomento: Bolsas no Brasil - Doutorado