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 -, - and -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, -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 -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.
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