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

Abstract

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.

Exploring the mechanism of an active ingredient of ginger, dihydrocapsaicin, on triple negative breast cancer based on network pharmacology and in vitro experiments

“…It was found to be cytotoxic to mouse and human TNBC cell lines 4T1 and MDA-MB-231 cells, arresting the cell cycle in the sub-G0 phase and inducing apoptosis ( 35 ). Liany used 6-gingerol-derived semi-synthetic compound SSi6 in a preclinical xenograft model to demonstrate that SSi6, as a single drug, has good anti-tumor activity in vivo without obvious side effects and can block the typical visceral organ metastasis of breast cancer, lymph node metastasis to the lungs and multiple organs ( 36 ). These documents and research results provide the basis and important reference for this study.…”

6-Gingerol attenuates subarachnoid hemorrhage-induced early brain injury via GBP2/PI3K/AKT pathway in the rat model

“…Among them, 6-gingerol, which is a major active phenolic compound extracted from ginger, attracted our interest. Previous studies demonstrated 6-gingerol to be a potent anti-tumor agent in a variety kind of tumors, including breast cancer ( Luna-Dulcey et al, 2021 ), gastric cancer ( Mansingh et al, 2018 ), lung cancer ( Tsai et al, 2020 ) and renal cell carcinoma ( Xu et al, 2020 ). Besides, 6-gingerol also exerted therapeutic effects in myocardial ischemia/reperfusion ( Lv et al, 2018 ; Lv et al, 2021 ), liver ( Hong et al, 2020 ) and cerebral ischemia/reperfusion injuries ( Liu et al, 2020 ; Luo J. et al, 2021 ).…”