[6]-Gingerol-Derived Semi-Synthetic Compound SSi6 Inhibits Tumor Growth and Metastatic Dissemination in Triple-Negative Breast Cancer Xenograft Models

Author(s)

Luna-Dulcey, Liany ^[1] ; da Silva, James Almada ^[2] ; Jimenez-Renard, Veronica ^[3] ; Caleiras, Eduardo ^[4] ; Mouron, Silvana ^[3] ; Quintela-Fandino, Miguel ^[3] ; Cominetti, Marcia R. ^[1]

Affiliation

^[1] Fed Univ Sao Carlos UFSCar, Dept Gerontol, Lab Biol Aging LABEN, BR-13565905 Sao Carlos, SP - Brazil

^[2] Fed Univ Sergipe UFS, Dept Pharm, Av Gov Marcelo Deda 330, BR-49400000 Lagarto, SE - Brazil

^[3] Spanish Natl Canc Res Ctr CNIO, Breast Canc Clin Res Unit, Madrid 28029 - Spain

^[4] Spanish Natl Canc Res Ctr CNIO, Histopathol Unit, Madrid 28029 - Spain

• Document type: Journal article
• Source: CANCERS; v. 13, n. 12 JUN 2021.
• Web of Science Citations: 0

Abstract

Simple Summary Triple-negative breast cancers (TNBC) represent approximately 15% of all breast cancers and lack the expression of a defined molecular target. This absence makes this subtype of cancer difficult to treat and control. Current chemotherapy drugs cause various side effects and toxicities that can jeopardize the quality of life of patients with TNBC cancer. Therefore, this research focuses on a new semi-synthetic compound derived from {[}6]-gingerol, where we demonstrate that it does not cause significant toxic effects in vivo and, more importantly, we demonstrate its antitumor and antimetastatic effects using preclinical xenograft models simulating two clinical scenarios of a woman with breast cancer. Breast cancer metastasis is the most common cause of cancer death in women worldwide. Triple-negative breast cancers (TNBC) form a heterogeneous group of tumors that have higher relapse rates and poorer survival compared to other breast cancer subtypes. Thus, this work reports the antitumor and antimetastatic activities of a {[}6]-gingerol-derived semi-synthetic compound named SSi6 on MDA-MB-231 TNBC cells using xenograft models. SSi6 did not cause toxic effects in vivo as demonstrated by body weight and hematological and histological evaluations. From the orthotopic xenograft model, we demonstrated that SSi6 slows and inhibits the growth of the primary tumor, as well as prevents metastatic spontaneous progression from lymph nodes to the lungs. Moreover, a second xenograft model with resection of the primary tumor showed that SSi6 also blocks the progression of metastases from the lymph nodes to other visceral organs. Taken together, our results demonstrate that SSi6 is a promising compound to be investigated in other preclinical and clinical models to be applied as a complementary therapy for TNBC. (AU)

• FAPESP's process: 19/12607-3 - Antitumor and antimetastatic effects of SSi6 in triple negative breast cancer using a Cell-line-Derived Xenograft model
• Grantee: Liany Johanna Luna Dulcey
• Support Opportunities: Scholarships abroad - Research Internship - Doctorate
• FAPESP's process: 18/05594-0 - Evaluation of the mechanism of action of SSi6 in the induction of autophagy and apoptosis in triple negative tumor cells: in vitro and in vivo studies
• Grantee: Liany Johanna Luna Dulcey
• Support Opportunities: Scholarships in Brazil - Doctorate
• FAPESP's process: 13/07600-3 - CIBFar - Center for Innovation in Biodiversity and Drug Discovery
• Grantee: Glaucius Oliva
• Support Opportunities: Research Grants - Research, Innovation and Dissemination Centers - RIDC