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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 type:Scholarships in Brazil - Doctorate
Effective date (Start): November 01, 2018
Effective date (End): September 30, 2021
Field of knowledge:Biological Sciences - Physiology
Principal Investigator:Márcia Regina Cominetti
Grantee:Liany Johanna Luna Dulcey
Home 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


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
(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)
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. Web of Science Citations: 0.
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. Web of Science Citations: 0.

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