An in vitro and in vivo antitumor mechanism of action evaluation of goniothalamin and its derivative, 2,4-dimethoxy-goniothalamin, in human breast cancer cells

• Grant number: 14/26033-5
• Support Opportunities: Scholarships abroad - Research Internship - Post-doctor
• Start date: April 01, 2015
• End date: March 31, 2016
• Field of knowledge: Biological Sciences - Pharmacology - General Pharmacology
• Principal Investigator: João Ernesto de Carvalho
• Grantee: Ana Paula Oliveira Hohne
• Supervisor: Atanasio Pandiella Alonso
• Host Institution: Centro Pluridisciplinar de Pesquisas Químicas, Biológicas e Agrícolas (CPQBA). Universidade Estadual de Campinas (UNICAMP). Paulínia , SP, Brazil
• Institution abroad: Universidad de Salamanca (USAL), Spain
• Associated to the scholarship: 13/15946-7 - Mechanism of antitumoral action of goniothalamin di-metoxy derivative and its mutagenicity and genotoxicity evaluation, BP.PD

Abstract

The dimethoxylated derivative of goniothalamin (diOMe-GTN), the target of the post-doctoral study of the candidate (FAPESP 2013/15946-7), showed promising in vitro antiproliferative activity for various tumor cell lines, in particular to those derived from human breast cancer MCF-7, MDA-MB-231 and MCF-7/BUS cells. Its effect on the cell cycle, as well as on the mechanism of cell death, on the proliferation of the cells under stimuli of hormones and its effects on the cell migration has been investigated and the results point to a pronounced antitumor activity. In order to continue the evaluation of its antitumor mechanism of action, we propose to evaluate its, and also goniothalamin, effect in human breast cancer (MCF-7) xenograft tumor model in rodents and also to investigate their effect in an in vitro resistance model with HER2-positive breast cancer (BT474 and SKBR3) cells. This evaluation will take genomic and proteomic approaches that should provide crucial information about the biological activity of GTN and diOMe-GTN, since, to the present time, there is just few information about their activities in breast cancer cells, and to identify the mechanisms by which these molecules act. This work has as partners Dr. Atanasio Pandiella, which has extensive experience in studies in breast cancer and animal testing, and the Centro de Investigación del Cáncer of the University of Salamanca (CSIC), Spain. (AU)