Fenugreek inhibits cathepsin G activity and suppresses the progression of malignant phenotypes in MCF-7 cells

Spices and herbs, which are derived from natural botanical sources, contain many bioactive compounds and play an important role in human health. The general and specific health benefits of these spices and herbs include anti-inflammatory, antioxidant, and anti-tumorigenic activities. Previously, we showed that cathepsin G, which is a neutrophil-derived serine protease localized in human breast cancer tissues, promotes cancer metastasis via induction of platelet-activating factor acetylhydrolase 1B2 (PAFAH1B2) expression in MCF-7 human breast cancer cells. Therefore, although regulation of cathepsin G activity is thought to be important in human breast cancer progression, no compounds that inhibit the activity have been identified for therapeutic purposes. In this study, we screened 50 spice and herb extracts. Peppermint, clove, Sichuan pepper, and fenugreek exhibited strong inhibitory effects on cathepsin G activity and suppressed cathepsin G-induced MCF-7 cell aggregation.; importantly, fenugreek suppressed the increase in PAFAH1B2 expression. The IC₅₀ of 37.38 μg/mL of fenugreek extract that showed inhibitory effect on cathepsin G-induced malignant progression was 5.87 times lower than the concentration that exerted cytotoxic effect. Interestingly, quercetin and trigonelline contained in fenugreek inhibited cathepsin G activity and suppressed the induction of cell aggregation and PAFAH1B2 expression in human breast cancer cells. These results suggest that quercetin and trigonelline are partly responsible for the inhibitory effect of fenugreek on cathepsin G-induced malignant progression of human breast cancer cells. Our findings provide a new breast cancer treatment strategy targeting cathepsin G, and fenugreek may have synergistic effects when combined with therapeutic drugs.