Eficácia do [10]-gingerol contra metástases de câncer de mama : estudos in vitro e in vivo em camundongos

Abstract

Breast cancer is the leading cause of death in Brazil and worldwide, between the types of cancer, triple negative TNBC (Triple Negative Breast Cancer), which do not express hormone receptors, represents 20% of the cases and presents relapses within 3 years. However, the major cause of death in cancer is due the formation of metastasis. The TNBC has a greater propensity to form lung and brain metastasis. Furthermore, currently few treatments are available. Search for new target treatments, with fewer side effects is very important to treat this disease. Natural products are rich sources of molecules with antitumoral activity; among them are the gingerols, from ginger and resveratrol, from grapes. Nevertheless, not much is known about antitumor activity of [10]-gingerol (10G). Therefore, the aim of this work was to investigate the potential use of 10G as an antimetastatic molecule in in vitro and in vivo experiments. In this work, 10G had antiproliferative activity on several breast cancer cell lines (4T1BM2, 4T1BM2 shRNAβ3, 4T1Br4, MDA-MB-231, MDA-MB-231 BrM) and on a normal cell line, bEnd.3. The natural compounds affected tumor cell morphology and RSVT was able to inhibit cell migration and adhesion through vitronectin. 10G induced apoptosis via the extrinsic pathway through the increase of caspase-9, -3 and -7 expression and decrease of Bcl-2 expression, induced cell cycle arrest in G1 and subG0 phase. In in vivo models, 10G inhibited primary tumor growth and lung metastasis, as well as bone and brain metastasis. Therefore, this study was able to provide new data as 10G can be acting in tumor cells and its possible clinical application.