Produção Nacional
[10]-gingerol induces apoptosis and inhibits metastatic dissemination of triple negative breast cancer in vivo
2017; Impact Journals LLC; Volume: 8; Issue: 42 Linguagem: Inglês
10.18632/oncotarget.20139
ISSN1949-2553
AutoresAna Carolina Baptista Moreno Martin, Angelina Maria Fuzer, Amanda Blanque Becceneri, James Almada da Silva, Rebeka Tomasin, Delphine Denoyer, Soo-Hyun Kim, Katherine McIntyre, Helen Pearson, Belinda Yeo, Aadya Nagpal, Xiawei Ling, Heloísa Sobreiro Selistre-de-Araújo, Paulo C. Vieira, Márcia R. Cominetti, Normand Pouliot,
Tópico(s)Hair Growth and Disorders
Resumo// Ana Carolina B.M. Martin 1, * , Angelina M. Fuzer 1, * , Amanda B. Becceneri 1 , James Almada da Silva 2 , Rebeka Tomasin 1 , Delphine Denoyer 3 , Soo-Hyun Kim 4 , Katherine A. McIntyre 5 , Helen B. Pearson 6 , Belinda Yeo 7 , Aadya Nagpal 7 , Xiawei Ling 4 , Heloisa S. Selistre-de-Araújo 8 , Paulo Cézar Vieira 2 , Marcia R. Cominetti 1, * and Normand Pouliot 4, 5, 7, * 1 Department of Gerontology, Federal University of São Carlos, São Carlos, SP, Brazil 2 Department of Chemistry, Federal University of São Carlos, São Carlos, SP, Brazil 3 Metals in Medicine Laboratory, Centre for Cellular and Molecular Biology (CCMB), Melbourne Burwood Campus, Deakin University, VIC, Australia 4 Department of Pathology and University of Melbourne, VIC, Australia 5 Sir Peter MacCallum Department of Oncology, University of Melbourne, VIC, Australia 6 European Cancer Stem Cell Research Institute, Cardiff University, Cathays, Cardiff, UK 7 Matrix Microenvironment and Metastasis Laboratory, Olivia Newton-John Cancer Research Institute, School of Cancer Medicine, La Trobe University, Heidelberg, Australia 8 Department of Physiological Sciences, Federal University of São Carlos, São Carlos, SP, Brazil * Authors contributed equally to this work and share co-senior authorship Correspondence to: Marcia R. Cominetti, email: mcominetti@ufscar.br Keywords: gingerol, breast cancer, cell cycle, apoptosis, animal models Received: January 23, 2017 Accepted: July 29, 2017 Published: August 10, 2017 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.
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