Screening of candidates to new antitumoral drugs by three-dimensional cell culture

• Grant number: 17/01287-2
• Support Opportunities: Scholarships in Brazil - Post-Doctoral
• Start date: July 01, 2017
• End date: April 30, 2023
• Field of knowledge: Biological Sciences - Morphology - Cytology and Cell Biology
• Principal Investigator: Márcia Regina Cominetti
• Grantee: Angelina Maria Fuzer
• Host Institution: Centro de Ciências Biológicas e da Saúde (CCBS). Universidade Federal de São Carlos (UFSCAR). São Carlos , SP, Brazil
• Associated research grant: 13/07600-3 - CIBFar - Center for Innovation in Biodiversity and Drug Discovery, AP.CEPID
• Associated scholarship(s): 19/25067-7 - Role of tumor-associated fibroblasts on the activity of potential anticancer compounds on lung and breast tumor cells in three-dimensional cell co-cultures, BE.EP.PD

Abstract

Breast cancer is a complex and multifactorial disease. The tumor microenvironment is an heterogenic environment with multiple interactions among tumor cells and other cell types which highly influence the tumor behavior. Several studies have revealed advantages of three-dimensional culture techniques (3D) over traditional two-dimensional monolayer cultures (2D). 3D cultures better mimic the tumor microenvironment found in vivo, as well as the interaction of cells with the extracellular matrix (ECM). Three-dimensional culture has produced different responses compared to those found in 2D cultures, such as increased resistance of tumor cells to various drugs, and increased selective sensitivity to tumor cells in relation to normal cells. The 3D cultures better mimic the tumor microenvironment found in vivo, as well as the interaction of cells with the extracellular matrix. Three-dimensional culture has produced different responses compared to those found in 2D cultures, such as increased resistance of tumor cells to various drugs, and increased selective sensitivity to tumor cells in relation to normal cells. The aim of this work is to apply new techniques for three-dimensional culture, learned in a world reference center (Bissell Lab - Lawrence Berkeley National Laboratory, California -USA) during the candidate's sandwich PhD, on screening of candidates to new antitumoral drugs in our laboratory. Previous results obtained during the stage using [10]-gingerol molecule have showed selectivity against malignant cells. The molecule was also able to revert the malignant phenotype and to induce apoptosis in this cell line. These new techniques will be used in our laboratory for the screening of candidate substances to new drugs with antitumor potential.

Scientific publications

(References retrieved automatically from Web of Science and SciELO through information on FAPESP grants and their corresponding numbers as mentioned in the publications by the authors)

BECCENERI, AMANDA BLANQUE; FUZER, ANGELINA MARIA; POPOLIN, CECILIA PATRICIA; CAZAL, CRISTIANE DE MELO; DOMINGUES, VANESSA DE CASSIA; FERNANDES, JOAO BATISTA; VIEIRA, PAULO CEZAR; COMINETTI, MARCIA REGINA. Acetylation of cedrelone increases its cytotoxic activity and reverts the malignant phenotype of breast cancer cells in 3D culture. Chemico-Biological Interactions, v. 316, JAN 25 2020. (17/01287-2, 12/25299-6, 14/25121-8)

BECCENERI, AMANDA B.; FUZER, ANGELINA M.; PLUTIN, ANA M.; BATISTA, ALZIR A.; LELIEVRE, SOPHIE A.; COMINETTI, MARCIA R.. Three-dimensional cell culture models for metallodrug testing: induction of apoptosis and phenotypic reversion of breast cancer cells by the trans-[Ru(PPh3)(2)(N,N-dimethyl-N-thiophenyl-thioureato-k(2)O,S)(bipy) ]PF6 complex. INORGANIC CHEMISTRY FRONTIERS, v. 7, n. 16, p. 2909-2919, AUG 21 2020. (17/01287-2, 18/19342-2, 13/07600-3, 17/20055-5, 15/24940-8, 14/25121-8)