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Effectiveness of structural changes in [10]-gingerol molecule in combination with the chemotherapeutic doxorubicin for the treatment of breast cancer: in vitro and in vivo studies. abstract

Grant number: 15/24940-8
Support type:Regular Research Grants
Duration: November 01, 2016 - April 30, 2019
Field of knowledge:Physical Sciences and Mathematics - Chemistry
Principal Investigator:Márcia Regina Cominetti
Grantee:Márcia Regina Cominetti
Home Institution: Centro de Ciências Biológicas e da Saúde (CCBS). Universidade Federal de São Carlos (UFSCAR). São Carlos , SP, Brazil
Assoc. researchers:Fernanda de Freitas Anibal ; Marco Antonio Barbosa Ferreira ; Paulo Cézar Vieira ; Renata Fonseca Vianna Lopez


Breast cancer is the leading cause of death in Brazil and worldwide. Triple negative breast cancer (TNBC), which does not express hormone receptors, comprises 20% of the breast cancer cases and presents relapses within 3 years, approximately. However, the major cause of death in cancer is due the formation of metastases. TNBC has a high incidence of lung and brain metastases. Moreover, few treatments are available for these patients, due to the lack of target therapies in this type of cancer as in tumors that express hormone receptors. Search and development of new treatments for TNBC with fewer side effects, more effective and with less resistance are important to treat this disease. Natural products are rich sources of molecules with antimetastatic and antitumoral activities. Among these molecules are the gingerols, from ginger. Natural products are also known to have chemosensitizing and radiosensitizing effects, resulting in a better treatment efficacy with fewer side effects. Previous results from our research group showed that among gingerols, [6]-, [8]- and [10]-gingerol, the latter is the molecule with the best antiproliferative activity in breast tumor cells with fewer effects on normal cells, human fibroblasts, indicating a selectivity for tumor cells. Furthermore, [10]-gingerol has an antitumoral activity, reducing primary tumor size in vivo, and also an antimetastatic activity, reducing lung, bones and brain metastases. Therefore, the aim of this project is to investigate structural modifications of [10]-gingerol (10GM) molecule to improve its activity and to verify its chemosensitizing effect in a combinatorial treatment with doxorubicin using an animal breast cancer spontaneous metastasis model. (AU)

Scientific publications (8)
(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)
REGINA MANZINE, PATRICIA; ETTCHETO, MIREN; CANO, AMANDA; BUSQUETS, ORIOL; MARCELLO, ELENA; PELUCCHI, SILVIA; DI LUCA, MONICA; ENDRES, KRISTINA; OLLOQUEQUI, JORDI; CAMINS, ANTONI; COMINETTI, MARCIA REGINA. ADAM10 in Alzheimer's disease: Pharmacological modulation by natural compounds and its role as a peripheral marker. BIOMEDICINE & PHARMACOTHERAPY, v. 113, MAY 2019. Web of Science Citations: 2.
ULIANA, CAROLINA V.; DE OLIVEIRA, TASSIA R.; COMINETTI, MARCIA R.; FARIA, RONALDO C. Label-free evaluation of small-molecule-protein interaction using magnetic capture and electrochemical detection. ANALYTICAL AND BIOANALYTICAL CHEMISTRY, v. 411, n. 10, p. 2111-2119, APR 2019. Web of Science Citations: 0.
NAVES, MARINA A.; GRAMINHA, ANGELICA E.; VEGAS, LEGNA C.; LUNA-DULCEY, LIANY; HONORATO, JOAO; MENEZES, ANTONIO C. S.; BATISTA, ALZIR A.; COMINETTI, MARCIA R. Transport of the Ruthenium Complex [Ru(GA)(dppe)(2)]PF6 into Triple-Negative Breast Cancer Cells Is Facilitated by Transferrin Receptors. MOLECULAR PHARMACEUTICS, v. 16, n. 3, p. 1167-1183, MAR 2019. Web of Science Citations: 0.
COMINETTI, MARCIA R.; ALTEI, WANESSA F.; SELISTRE-DE-ARAUJO, HELOISA SOBREIRO. Metastasis inhibition in breast cancer by targeting cancer cell extravasation. BREAST CANCER-TARGETS AND THERAPY, v. 11, p. 165-178, 2019. Web of Science Citations: 0.
FUZER, ANGELINA M.; MARTIN, ANA C. B. M.; BECCENERI, AMANDA B.; DA SILVA, JAMES A.; VIEIRA, PAULO C.; COMINETTI, MARCIA R. [10]-Gingerol Affects Multiple Metastatic Processes and Induces Apoptosis in MDA-MB-231 Breast Tumor Cells. ANTI-CANCER AGENTS IN MEDICINAL CHEMISTRY, v. 19, n. 5, p. 645-654, 2019. Web of Science Citations: 1.
BECCENERI, AMANDA BLANQUE; POPOLIN, CECILIA PATRICIA; MARIA PLUTIN, ANA; MAISTRO, EDSON LUIS; CASTELLANO, EDUARDO ERNESTO; BATISTA, ALZIR AZEVEDO; COMINETTI, MARCIA REGINA. The trans-[Ru(PPh3)(2)(N,N-dimethyl-N `-thiophenylthioureato-k(2)O,S)(bipy)] PF6 complex has pro-apoptotic effects on triple negative breast cancer cells and presents low toxicity in vivo. Journal of Inorganic Biochemistry, v. 186, p. 70-84, SEP 2018. Web of Science Citations: 2.
MARTIN, ANA CAROLINA B. M.; FUZER, ANGELINA M.; BECCENERI, AMANDA B.; DA SILVA, JAMES ALMADA; TOMASIN, REBEKA; DENOYER, DELPHINE; KIM, SOO-HYUN; MCINTYRE, KATHERINE A.; PEARSON, HELEN B.; YEO, BELINDA; NAGPAL, AADYA; LING, XIAWEI; SELISTRE-DE-ARAUJO, HELOISA S.; VIEIRA, PAULO CEZAR; COMINETTI, MARCIA R.; POULIOT, NORMAND. [10]-gingerol induces apoptosis and inhibits metastatic dissemination of triple negative breast cancer in vivo. ONCOTARGET, v. 8, n. 42, p. 72260-72271, SEP 22 2017. Web of Science Citations: 10.
POPOLIN, CECILIA P.; REIS, JOAO P. B.; BECCENERI, AMANDA B.; GRAMINHA, ANGELICA E.; ALMEIDA, MARCIO A. P.; CORREA, RODRIGO S.; COLINA-VEGAS, LEGNA A.; ELLENA, JAVIER; BATISTA, ALZIR A.; COMINETTI, MARCIA R. Cytotoxicity and anti-tumor effects of new ruthenium complexes on triple negative breast cancer cells. PLoS One, v. 12, n. 9 SEP 12 2017. Web of Science Citations: 9.

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Filed patent(s) as a result of this research project

Solicitação em análise e dentro do prazo legal de sigilo previsto na legislação BR1020180727478 - Universidade Federal de São Carlos (UFSCAR) . Solicitação em análise e dentro do prazo legal de sigilo previsto na legislação - November 2018, 05

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