Sulforaphene Derivatived As A Potential Anti-Tumor Agent With Special Mechanisms

Epidemiology and tumor studies in vivo and in vitro have confirmed that isothiocyanate(ITCs),especially sulforaphane(SFA) which occurs naturally in cruciferous plants,can take effects during the "pre-initiation" and "post-initiation" phase of cancer through several distinct mechanisms.In our previous study,we’ve successfully extracted and purified a SFA analogue,called sulforaphene(SFE).In this study,we evaluated the antitumor activity in vitro and in vivo of SFE towards the esophageal squamous cell carcinoma(ESCC)and breast cancer commonly happened in Chinese populations,and investigated the molecular mechanism of SFE in these two types of cancer.Methods:in vitro experiment, we use MTT method and trypan blue staining method to evaluate the antitumor activity of SFE.Effects of SFE on the cell cycle and cell apoptosis were measured by flow cytometry. We use Western Blot to analyse the expression and phosphorylation level of biomarkers related to the DNA damage and cell cycle transition.Gene expression profiles of tumor cells before and after the SFE treatment were studied using gene chip technology.Gene overexpression plasmid were transiently transfected into tumor cells to observe the function of gene towards tumor growth.Xenograft models shows the anti-breast cancer activity and toxicity in vivo.Results.SFE can effectively inhibit the ESCC and breast cancer cells growth as none of 48hr IC50 were more than 25μM. Flow cytometry shows that SFE can both induce cell cycle arrest and apotosis in ESCC cells, which may be related to DNA damage caused by SFE,especially double strand break(DSB).At the same time, accumulation of intracellular reactive oxygen species (ROS) partly contribute to the anticancer effect of SFE to ESCC cells.Gene expression profile analysis found that EGR1 gene expression were upregulated 18 times after the treatment of 15μM SFE for 48hr,and the upregulated expression of EGR1 gene can inhibit the growth of breast cancer cells.Survival curve analysis showed that breast cancer patients with high expression of EGR1 have a relatively longer survival(HR=0.76,p=3.5e×10-6).EGR1 protein could be an important target protein by SFE to inhibit breast cancer cells. These results suggest that the natural product SFE is a promising monomer compounds for fighting ESCC and breast cancer.