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 Opportunities: Regular Research Grants
• Start date: November 01, 2016
• End date: April 30, 2019
• Field of knowledge: Physical Sciences and Mathematics - Chemistry - Organic Chemistry
• Principal Investigator: Márcia Regina Cominetti
• Grantee: Márcia Regina Cominetti
• Host Institution: Centro de Ciências Biológicas e da Saúde (CCBS). Universidade Federal de São Carlos (UFSCAR). São Carlos , SP, Brazil
• Associated researchers: Fernanda de Freitas Anibal ; Marco Antonio Barbosa Ferreira ; Paulo Cézar Vieira ; Renata Fonseca Vianna Lopez

Abstract

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

(19)

(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)

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. (13/00798-2, 15/24940-8, 14/25121-8)

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. (13/00798-2, 16/23202-6, 15/24940-8)

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. (13/00798-2, 15/24940-8)

GRAMINHA, ANGELICA E.; HONORATO, JOAO; CORREA, RODRIGO S.; COMINETTI, MARCIA R.; MENEZES, ANTONIO C. S.; BATISTA, ALZIR A.. A novel ruthenium(II) gallic acid complex disrupts the actin cytoskeleton and inhibits migration, invasion and adhesion of triple negative breast tumor cells. DALTON TRANSACTIONS, v. 50, n. 1, p. 323-335, JAN 7 2021. (14/19632-0, 16/16312-0, 15/24940-8, 13/07600-3)

GROSSO NEVES, LIA MARA; PARIZOTTO, NIVALDO ANTONIO; TIM, CARLA ROBERTA; FLORIANO, ELAINE MEDEIROS; VIANNA LOPEZ, RENATA F.; VENANCIO, TIAGO; FERNANDES, JOAO BATISTA; COMINETTI, MARCIA REGINA. Polysaccharide-rich hydrogel formulation combined with photobiomodulation repairs UV-induced photodamage in mice skin. WOUND REPAIR AND REGENERATION, v. 28, n. 5, p. 11-pg., 2020-06-26. (13/27021-8, 12/25299-6, 15/24940-8)

TOMASIN, REBEKA; BAPTISTA MORENO MARTIN, ANA CAROLINA; COMINETTI, MARCIA REGINA. Metastasis and cachexia: alongside in clinics, but not so in animal models. JOURNAL OF CACHEXIA SARCOPENIA AND MUSCLE, v. 10, n. 6, p. 12-pg., 2019-08-22. (15/24940-8, 16/23202-6)

GROSSO NEVES, LIA MARA; TIM, CARLA ROBERTA; FLORIANO, ELAINE MEDEIROS; DA SILVA DE AVO, LUCIMAR RETTO; FERNANDES, JOAO BATISTA; PARIZOTTO, NIVALDO ANTONIO; COMINETTI, MARCIA REGINA. Lycium barbarumpolysaccharide fraction associated with photobiomodulation protects from epithelium thickness and collagen fragmentation in a model of cutaneous photodamage. Lasers in Medical Science, v. 36, n. 4, AUG 2020. (12/25299-6, 13/27021-8, 15/24940-8)

GRAMINHA, ANGELICA E.; HONORATO, JOAO; DULCEY, LIANY LUNA; GODOY, LUANI REZENDE; BARBOSA, MARILIA F.; COMINETTI, MARCIA R.; MENEZES, ANTONIO C.; BATISTA, ALZIR A.. Evaluation of the biological potential of ruthenium(II) complexes with cinnamic acid. Journal of Inorganic Biochemistry, v. 206, MAY 2020. (14/19632-0, 15/24940-8, 16/16312-0)

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. (16/16312-0, 15/24940-8, 13/00798-2)

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. (15/24940-8, 14/22401-0, 15/19890-1)

GROSSO NEVES, LIA MARA; PARIZOTTO, NIVALDO ANTONIO; TIM, CARLA ROBERTA; FLORIANO, ELAINE MEDEIROS; VIANNA LOPEZ, RENATA F.; VENANCIO, TIAGO; FERNANDES, JOAO BATISTA; COMINETTI, MARCIA REGINA. Polysaccharide-rich hydrogel formulation combined with photobiomodulation repairs UV-induced photodamage in mice skin. WOUND REPAIR AND REGENERATION, JUN 2020. (13/27021-8, 15/24940-8, 12/25299-6)

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; et al. [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. (12/03771-5, 13/00798-2, 15/24940-8, 12/18908-6)

TOMASIN, REBEKA; MARTIN, ANA CAROLINA BAPTISTA MORENO; COMINETTI, MARCIA REGINA. Metastasis and cachexia: alongside in clinics, but not so in animal models. JOURNAL OF CACHEXIA SARCOPENIA AND MUSCLE, AUG 2019. (15/24940-8, 16/23202-6)

BECCENERI, AMANDA B.; FUZER, ANGELINA M.; PLUTIN, ANA M.; BATISTA, ALZIR A.; LELIEVRE, SOPHIE A.; COMINETTI, MARCIA R.. Three-dimensional cell culture models for metallodrug testing: induction of apoptosis and phenotypic reversion of breast cancer cells by the trans-[Ru(PPh3)(2)(N,N-dimethyl-N-thiophenyl-thioureato-k(2)O,S)(bipy) ]PF6 complex. INORGANIC CHEMISTRY FRONTIERS, v. 7, n. 16, p. 2909-2919, AUG 21 2020. (17/01287-2, 18/19342-2, 13/07600-3, 17/20055-5, 15/24940-8, 14/25121-8)

BAPTISTA MORENO MARTIN, ANA CAROLINA; TOMASIN, REBEKA; LUNA-DULCEY, LIANY; GRAMINHA, ANGELICA ELEN; NAVES, MARINA ARAUJO; GOMES TELES, RAMON HANDERSON; DA SILVA, VINICIUS DUVAL; DA SILVA, JAMES ALMADA; VIEIRA, PAULO CEZAR; ANNABI, BORHANE; et al. [10]-Gingerol improves doxorubicin anticancer activity and decreases its side effects in triple negative breast cancer models. CELLULAR ONCOLOGY, v. 43, n. 5, AUG 2020. (15/24940-8, 16/23202-6)

REGINA MANZINE, PATRICIA; ETTCHETO, MIREN; CANO, AMANDA; BUSQUETS, ORIOL; MARCELLO, ELENA; PELUCCHI, SILVIA; DI LUCA, MONICA; ENDRES, KRISTINA; OLLOQUEQUI, JORDI; CAMINS, ANTONI; et al. ADAM10 in Alzheimer's disease: Pharmacological modulation by natural compounds and its role as a peripheral marker. BIOMEDICINE & PHARMACOTHERAPY, v. 113, MAY 2019. (17/13224-5, 15/24940-8, 15/26084-1)

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. (15/24940-8, 13/00798-2)

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; et al. [10]-gingerol induces apoptosis and inhibits metastatic dissemination of triple negative breast cancer invivo. ONCOTARGET, v. 8, n. 42, p. 12-pg., 2017-09-22. (13/00798-2, 12/18908-6, 15/24940-8, 12/03771-5)

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. 15-pg., 2018-09-01. (13/00798-2, 14/25121-8, 15/24940-8)

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