ISSN print edition: 0366-6352 ISSN electronic edition: 1336-9075 Registr. No.: MK SR 9/7 Published monthly

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

Giovana Bicudo Gomes, Claudia Stutz Zubieta, Simone Schneider Weber, Dênis Pires de Lima, Thatikonda Narendar Reddy, Ana Tereza Gomes Guerrero, Maria de Fatima Cepa Matos, Eduardo Benedetti Parisotto, and Renata Trentin Perdomo

Laboratório de Biologia Molecular e Cultura de Células, Faculdade de Ciências Farmacêuticas, Alimentos e Nutrição, Universidade Federal de Mato Grosso do Sul, Campo Grande, Brazil

E-mail: eduardo.parisotto@ufms.br

Received: 29 July 2020  Accepted: 29 September 2020

Abstract:

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.

Keywords: Thiopyrimidine derivatives; 3D-cultured; Cancer; Oxidative stress

Full paper is available at www.springerlink.com.

DOI: 10.1007/s11696-020-01383-z

Chemical Papers 75 (3) 1211–1220 (2021)