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Thiopyrimidine derivatives induce cytotoxicity, cell cycle arrest and oxidative stress in breast cancer 3D-spheroids

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3D-cultured breast cancer cells had shown relative drug resistance as compared to 2D-cultured cells, and it has been suggested as a new in vitro cell-based drug-testing platform to look for novel antitumor molecule. Given the complexity of in vivo tumors and relative drug resistance, we evaluated a promising approach of cell cancer culture looking for potential antitumor molecules. In this study, we have proposed to investigate the 3D tumor breast cancer spheroid response to two thiopyrimidine derivatives (BUC and PEC) previously tested on monolayer culture. The evaluated compounds were synthetized from cashew nutshell liquid (CNSL). Cytotoxic, antiproliferative and pro-apoptotic properties were determined in the 2D-cultured cells. Cell viability, cell cycle analyses and oxidative stress markers of 3D-spheroids were determined. Results demonstrate the cytotoxic and antiproliferative effects of these thiopyrimidine derivatives. Additionally, BUC and PEC treatment on breast cancer 3D-spheroids induced oxidative stress and cell cycle arrest in the G1 phase. Both the tested compounds induced cytotoxicity, antiproliferative effects, oxidative stress and cell cycle arrest in breast cancer 3D-spheroids and could be considered for antitumor potential in further study as treatment strategy.

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The authors would like to thank FUNDECT—Fundação de Apoio ao Desenvolvimento do Ensino, Ciência e Tecnologia do Estado de Mato Grosso do Sul, CNPq—Conselho Nacional de Desenvolvimento Científico e Tecnológico and Coordenação de Aperfeiçoamento de Pessoal de Nível Superior—Brasil (CAPES)—Finance Code 001.

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Correspondence to Eduardo Benedetti Parisotto or Renata Trentin Perdomo.

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Gomes, G.B., Zubieta, C.S., Weber, S.S. et al. Thiopyrimidine derivatives induce cytotoxicity, cell cycle arrest and oxidative stress in breast cancer 3D-spheroids. Chem. Pap. 75, 1211–1220 (2021).

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