[10]-gingerol induces apoptosis and inhibits metastatic dissemination of triple negative breast cancer invivo

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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

• Document type: Journal article
• Source: ONCOTARGET; v. 8, n. 42, p. 12-pg., 2017-09-22.

Abstract

There is increasing interest in the use of non-toxic natural products for the treatment of various pathologies, including cancer. In particular, biologically active constituents of the ginger oleoresin (Zingiber officinale Roscoe) have been shown to mediate anti-tumour activity and to contribute to the anti-inflammatory, antioxidant, antimicrobial, and antiemetic properties of ginger. Here we report on the inhibitory properties of [10]-gingerol against metastatic triple negative breast cancer (TNBC) in vitro and in vivo. We show that [10]-gingerol concentration-dependently induces apoptotic death in mouse and human TNBC cell lines in vitro. In addition, [10]-gingerol is well tolerated in vivo, induces a marked increase in caspase-3 activation and inhibits orthotopic tumour growth in a syngeneic mouse model of spontaneous breast cancer metastasis. Importantly, using both spontaneous and experimental metastasis assays, we show for the first time that [10]-gingerol significantly inhibits metastasis to multiple organs including lung, bone and brain. Remarkably, inhibition of brain metastasis was observed even when treatment was initiated after surgical removal of the primary tumour. Taken together, these results indicate that [10]-gingerol may be a safe and useful complementary therapy for the treatment of metastatic breast cancer and warrant further investigation of its efficacy, either alone or in combination with standard systemic therapies, in pre-clinical models of metastatic breast cancer and in patients. (AU)

• FAPESP's process: 13/00798-2 - The extracellular matrix in aging, exercise and in the tumor microenvironment
• Grantee: Heloisa Sobreiro Selistre de Araújo
• Support Opportunities: Research Projects - Thematic Grants
• FAPESP's process: 12/18908-6 - Cellular and molecular mechanisms involved in the antiproliferative action of [10]-gingerol on breast tumor cells
• Grantee: Angelina Maria Fuzer
• Support Opportunities: Scholarships in Brazil - Doctorate (Direct)
• FAPESP's process: 15/24940-8 - 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
• Grantee: Márcia Regina Cominetti
• Support Opportunities: Regular Research Grants
• FAPESP's process: 12/03771-5 - Identification of metastasis suppressor genes
• Grantee: Rebeka Tomasin
• Support Opportunities: Scholarships abroad - Research Internship - Doctorate