Although inhibition of mammary tumorigenesis by isothiocyanates has been widely studied, little is known about the effects of sulforaphene on invasiveness of breast cancer. Here, sulforaphene significantly inhibited the migration and invasion of triple-negative SUM159 human breast cancer cells and suppressed the expression and activity of matrix metalloproteinases 2 and 9 (MMP-2 and MMP-9). The Hedgehog (Hh) pathway, as an upstream signaling modulator, was significantly suppressed by sulforaphene. In particular, ciliary localization of Gli1 and its nuclear translocation were blocked by sulforaphene in a time-dependent manner. Consistently, downregulation of Hh signaling by vismodegib and Gli1 knockdown reduced the cellular migration and invasion as well as the expression of MMP-2 and MMP-9. These results indicate that the suppression of Hh/Gli1 signaling by sulforaphene may reduce the MMP-2 and MMP-9 activities and cellular invasiveness of human breast cancer cells, suggesting the potential efficacy of sulforaphene against breast cancer invasion and metastasis.

Sulforaphane significantly (p<0.05) inhibited tumor necrosis factor (TNF)-α induced cellular migration and invasion in MCF10DCIS.com human breast cancer cells, compared with controls. mRNA and protein expressions of MMPs, including MMP-2, MMP-9, and MMP-13, and the enzymatic activities of MMP-2 and MMP-9 were suppressed by sulforaphane treatments at 1, 5, and 10 µM concentration in MCF10DCIS.com cells. Sulforaphane should be considered as a potent agent for retardation of mammary tumorigenesis.

To provide a platform for evaluating significant interactions contributing to the enhanced physiological efficacy and reduced hepatotoxicity, we used a robust design to determine the optimal combination of six major green tea catechins, epigallocatechin gallate (EGCG), epigallocatechin (EGC), epicatechin gallate (ECG), epicatechin (EC), gallocatechin, and catechin. Based on the mixture design, 28 experiments were performed to inhibit nitric oxide (NO) in RAW 264.7 cells and hepatotoxicity in Chang liver cells. Significant candidates, EGCG, EC, gallocatechin and catechin, were selected after optimization. The combination showing simultaneous enhancement of NO inhibition and reduction of hepatotoxicity was EGCG and gallocatechin at a ratio of 0.65 to 0.35 by surface response methodology and desirability function, through which their co-treatment was validated. Here, we describe a platform for simultaneously determining the optimized combination of natural components exerting enhanced efficacy and reduced toxicity.