Abstract B40: [10]-gingerol as a pro-apoptotic molecule in triple negative breast cancer

Abstract

Abstract The aim of this work was to study the pro-apoptotic effects of [10]-gingerol and connect them to anti-tumor and anti-metastatic activities in triple negative breast cancer (TNBC) cell lines and in an spontaneous triple negative breast cancer model in vivo. Breast cancer has the highest incidence among women and metastasis is the major cause of death in cancer. TNBC affects 20% of women with breast cancer. This cancer type is very aggressive and has a high propensity to form lung and brain metastases. Nowadays, there is no effective treatment for TNBC and therefore, new therapies are required. Studies to discovery new molecules to be used in more efficient treatments for this disease are essential. Molecules that can interfere with cell proliferation, migration, invasion, apoptosis and cell cycle can be used as a model or tools to develop new anti-metastatic drugs. Epidemiologic studies have shown that Asian populations have lower incidence of breast cancer comparing to western populations. This has been attributed in part to differences in dietary habits. In particular, gingerols, natural compounds extracted from ginger rhizomes, have been shown to present anti-cancer properties against various tumor cell types in vitro and in vivo. MTT assay was performed to verify the inhibitory effects of [10]-gingerol on cell proliferation. To investigate [10]-gingerol mechanisms of action, apoptosis, cell cycle assays and TUNEL (Terminal deoxynucleotidyl transferase dUTP nick end labeling) were performed. For the in vivo data an spontaneous model of breast cancer metastasis was used. Results: [10]-gingerol was able to inhibit cell proliferation in different cell lines. In the murine cell line (4T1Br4), [10]-gingerol induced apoptosis, cell cycle arrest at sub-G0 phase and also induced DNA damage demonstrated by TUNEL assay, therefore interfering with DNA and provoking its damage. [10]-gingerol inhibited lung, bone and brain metastases in an intra-mammary fat pad spontaneous breast cancer model. Conclusion: [10]-gingerol showed to be a non-toxic compound with anti-proliferative and DNA damaging effects, inducing cell apoptosis in vitro and also inhibiting lung, bone and brain metastases in a spontaneous TNBC model in vivo. Patent deposit: BR 10 2015 024093 7. Approved by ethical committee – E507 and 3224-1. Citation Format: Ana Carolina B. M. Martin, Rebeka Tomasin, Amanda Blanque Becceneri, Angelina Fuzer, Paulo Cezar Vieira, Marcia Regina Cominetti. [10]-gingerol as a pro-apoptotic molecule in triple negative breast cancer [abstract]. In: Proceedings of the AACR Special Conference on DNA Repair: Tumor Development and Therapeutic Response; 2016 Nov 2-5; Montreal, QC, Canada. Philadelphia (PA): AACR; Mol Cancer Res 2017;15(4_Suppl):Abstract nr B40.