SENSITIZER EFFECTS AND MECHANISMS OF ACTION OF [10]-GINGEROL IN COMBINATION WITH DOXORUBICIN FOR BREAST CANCER TREATMENT: IN VITRO AND IN VIVO STUDIES

• Grant number: 16/23202-6
• Support type: Scholarships in Brazil - Post-Doctorate
• Effective date (Start): February 01, 2018
• Effective date (End): February 28, 2021
• Field of knowledge: Biological Sciences - Morphology - Cytology and Cell Biology
• Principal researcher: Márcia Regina Cominetti
• Grantee: Ana Carolina Baptista Moreno Martin
• Home Institution: Centro de Ciências Biológicas e da Saúde (CCBS). Universidade Federal de São Carlos (UFSCAR). São Carlos , SP, Brazil

Abstract

Breast cancer is the leading cause of death in Brazil and worldwide. Triple negative breast cancer (TNBC), characterized by the lack of hormone receptors expression, does not respond to current target therapies and few treatments are available for these patients. Moreover, the major cause of cancer deaths is due to metastases that are resistant to therapy. TNBC has a high incidence of lung and brain metastases. Search and development of new treatments for TNBC with increased effectiveness, less side effects, and that can overcome resistance are essential to treat this disease. Natural products are rich sources of molecules with antimetastatic and antitumor activities. Among these molecules are the gingerols, from ginger. Additionally, natural products are known to have chemosensitizing and radiosensitizing effects, resulting in better treatment efficacy and less side effects. Previous results from our research group has shown that among gingerols [6]-, [8]- and [10]-gingerol, the last one is the molecule with the best antiproliferative activity in human breast tumor cells with less effects on normal cells (human fibroblasts), indicating selectivity for tumor cells. Furthermore, [10]-gingerol has in vivo antitumor activity, reducing primary tumor size, and an antimetastatic activity, reducing lung, bones and brain metastases. Therefore, the aim of this project is to investigate the synergetic association of [10]-gingerol with doxorubicin, a standard chemotherapy used in the clinic, and verify its chemosensitizer, antitumor and antimetastatic activities, and the possible mechanisms of action involved in this process, using a breast cancer spontaneous metastasis model.

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)

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

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)

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)