Evaluation of the mechanism of action of SSi6 in the induction of autophagy and apoptosis in triple negative tumor cells: in vitro and in vivo studies

• Grant number: 18/05594-0
• Support Opportunities: Scholarships in Brazil - Doctorate
• Start date: November 01, 2018
• End date: September 30, 2021
• Field of knowledge: Biological Sciences - Physiology
• Principal Investigator: Márcia Regina Cominetti
• Grantee: Liany Johanna Luna Dulcey
• Host Institution: Centro de Ciências Biológicas e da Saúde (CCBS). Universidade Federal de São Carlos (UFSCAR). São Carlos , SP, Brazil
• Associated scholarship(s): 19/12607-3 - Antitumor and antimetastatic effects of SSi6 in triple negative breast cancer using a Cell-line-Derived Xenograft model, BE.EP.DR

Abstract

Breast Cancer represents the most prevalent type of Cancer in women, accounting for about 25% of all cancers diagnosed in women. Among the different subtypes of this disease, Triple Negative Breast Cancer is considered the most aggressive and the worst prognosis of survival, since it does not have a specific therapeutic target. Currently, many drugs are available in the market for the treatment of this type of Cancer, however, most of these drugs are poorly selective (cause damage to the DNA of normal and tumor cells), leading to the various known side effects of current chemotherapy. Therefore, the development of new, more selective antitumor drugs to eliminate or inhibit the growth of neoplastic cells is one of the major challenges in this area. In this sense, several current research has been using chemically modified natural products (semi-synthetic compounds) in the treatment of several types of Cancer, in order to improve the selectivity and activity of these compounds. Gingerois (extracted from ginger rhizome) are biologically active molecules well studied in the literature for their properties of clinical and therapeutic interest. Among these compounds, [6] -gendererol (6G) is notable for its antitumor properties against different types of Cancer, including Breast Cancer. Thus, a new compound (SSi6) was synthesized by modifying 6G with 2,4-dinitrophenylhydrazone-acetone and will be tested for the treatment of this subtype of Cancer. Thus, this project aims to determine the mechanism of action of SSi6 in MDA-MB-231 cells, in addition to determining the antitumor and antimetastatic effects in vivo in the mouse breast tumor line 4T1.13ch5T1 using a model of spontaneous metastasis. (AU)

Scientific publications

(4)

(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)

LUNA-DULCEY, LIANY; DA SILVA, JAMES ALMADA; JIMENEZ-RENARD, VERONICA; CALEIRAS, EDUARDO; MOURON, SILVANA; QUINTELA-FANDINO, MIGUEL; COMINETTI, MARCIA R.. [6]-Gingerol-Derived Semi-Synthetic Compound SSi6 Inhibits Tumor Growth and Metastatic Dissemination in Triple-Negative Breast Cancer Xenograft Models. CANCERS, v. 13, n. 12, JUN 2021. (19/12607-3, 18/05594-0, 13/07600-3)

DE OLIVEIRA, TAMIRES D.; PLUTIN, ANA M.; LUNA-DULCEY, LIANY; CASTELLANO, EDUARDO E.; COMINETTI, MARCIA R.; BATISTA, ALZIR A.. Cytotoxicity of ruthenium-N,N-disubstituted-N '-acylthioureas complexes. Materials Science & Engineering C-Materials for Biological Applications, v. 115, p. 11-pg., 2020-10-01. (18/05594-0)

DE OLIVEIRA, TAMIRES D.; PLUTIN, ANA M.; LUNA-DULCEY, LIANY; CASTELLANO, EDUARDO E.; COMINETTI, MARCIA R.; BATISTA, ALZIR A.. Cytotoxicity of ruthenium-N,N-disubstituted-N `-acylthioureas complexes. Materials Science & Engineering C-Materials for Biological Applications, v. 115, OCT 2020. (18/05594-0, 18/19342-2)

LUNA-DULCEY, LIANY; DA SILVA, JAMES A.; COMINETTI, MARCIA R.. SSi6 promotes cell death by apoptosis through cell cycle arrest and inhibits migration and invasion of MDA-MB-231 human breast cancer cells. ANTI-CANCER DRUGS, v. 31, n. 1, p. 35-43, JAN 2020. (13/07600-3, 18/05594-0)