New 3-alkylpyridine marine alkaloid analogues as promising antitumor agents against the CD44 +/high /CD24 -/low subset of triple-negative breast cancer cell line.

Autor: de Lima AB; Serviço de Biologia Celular, Fundação Ezequiel Dias, Belo Horizonte, MG, Brazil., Barbosa CS; Núcleo de Pesquisa em Química Biológica (NQBio), Universidade Federal de São João del Rei, Divinópolis, MG, Brazil., Gonçalves AMMN; Núcleo de Pesquisa em Química Biológica (NQBio), Universidade Federal de São João del Rei, Divinópolis, MG, Brazil., Santos FVD; Núcleo de Pesquisa em Química Biológica (NQBio), Universidade Federal de São João del Rei, Divinópolis, MG, Brazil., Viana GHR; Núcleo de Pesquisa em Química Biológica (NQBio), Universidade Federal de São João del Rei, Divinópolis, MG, Brazil., Varotti FP; Núcleo de Pesquisa em Química Biológica (NQBio), Universidade Federal de São João del Rei, Divinópolis, MG, Brazil., Silva LM; Serviço de Biologia Celular, Fundação Ezequiel Dias, Belo Horizonte, MG, Brazil.
Jazyk: angličtina
Zdroj: Chemical biology & drug design [Chem Biol Drug Des] 2017 Jul; Vol. 90 (1), pp. 5-11. Date of Electronic Publication: 2017 Feb 07.
DOI: 10.1111/cbdd.12923
Abstrakt: Triple-negative breast cancer (TNBC) is one of the most aggressive cancers in women. Additionally, presence of residual cancer stem cells (CSC) in TNBC has challenged the efficacy of chemotherapy. Thus, the development of new molecules with potential action against CSC is fundamental. In this study, six synthetic analogues of theonelladin C, a 3-alkylpyridine marine alkaloid, were tested for cytotoxic activity against human TNBC cell line (BT-549) and tumorspheres derived from BT-549. Cytotoxicity assay was performed by sulforhodamine B (SRB). BT-549 and tumorspheres were examined for CD44 +/high /CD24 -/low markers, indicative of CSC profile, by flow cytometry. Clonogenic assay was performed to verify inhibiting growth of tumorspheres by the synthetic analogues. Cell death by apoptosis was investigated employing annexin V assay. SRB assay on BT-549 cells revealed that compounds 1c and 2c were the most active of the series, with IC 50 values of 18.66 and 9.8 μm, respectively. Compounds 1c and 2c were able to reduce both CSC-like population (CD44 +/high /CD24 -/low ) and non-CSC population (CD44 +/high /CD24 +/high ) in tumorsphere model. Clonogenic and annexin V assays confirmed the ability of 1c and 2c to induce growth inhibition and apoptosis in BT-549 cells and tumorspheres. These preliminary data indicate that these compounds are a promising class for development of anticancer agents.
(© 2016 John Wiley & Sons A/S.)
Databáze: MEDLINE
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