Methanolic Fenugreek Seed Extract Induces p53-Dependent Mitotic Catastrophe in Breast Cancer Cells, Leading to Apoptosis

PURPOSE: The plant Trigonella foenum-graecum, well-known as fenugreek, has been shown to control type-2 diabetes, the level of cholesterol, inflammation of wounds, disorders related to gastrointestinal tracts, and cancer as well. The present study aimed to evaluate the anti-cancer potential of methanolic fenugreek seed extract (FSE) and its possible molecular mechanism of action in breast cancer cells. METHODS: The anticancer potential of FSE was evaluated in MCF-7 and SK-BR3 breast cancer cells through various cellular assays after selecting the IC(10), IC(25), IC(35), and IC(50) doses by the cell cytotoxicity assay. Furthermore, the oral acute toxicity of FSE was examined in mice, according to the guidelines of the Organization for Economic Co-operation and Development (OECD). RESULTS: FSE exhibited dose-dependent cytotoxicity, as the IC(50) was found to be 150 and 40 μg/mL for MCF-7 and SK-BR3 breast cancer cells, respectively. The cytological observations showed the typical apoptotic morphology in both of the breast cancer cells upon treatment with FSE, as it inhibited the migration and adhesion, in a dose-dependent manner. The flow cytometry analysis revealed that FSE induced a significant shift from G(2)/M, and polyploidy (>G) at higher concentrations that suggested the activation of p53-mediated mitotic catastrophe, consequently leading to apoptosis. FSE induced a significant increase in the mitochondrial depolarization, ROS as well as a Bax/Bcl-2 ratio, and also exhibited the mitochondrial associated p53 signaling pathway. The in vivo acute toxicity data revealed that the oral administration of FSE did not induce any toxic effect in mice. CONCLUSION: This study, for the first time, reports the mechanistic details of the anti-cancer potential of FSE. It requires a detailed analysis to understand the effect of FSE to induce the apoptosis through the multiple signaling pathways at varying concentrations. The nontoxic effect of FSE in mice suggests to utilize it safely for pharmaceutical formulations in different cancer systems.