Capparis zeylanica L. root extract promotes apoptosis and cell cycle arrest, inhibits epithelial-to-mesenchymal transition and triggers E-cadherin expression in breast cancer cell lines.

Abstract

Capparis zeylanica L. is a climbing shrub distributed in Indian subcontinent and Mediterranean region. Almost all parts of the plant are used in folk medicine and traditional practices to treat several human ailments. The present study was aimed to investigate the role of C. zeylanica L. root extract in preventing cancerous cells growth and proliferation, as well as promoting apoptosis and cell cycle arrest in MDA-MB-231 and MCF-7 breast cancer cells. Methanolic extract of C. zeylanica L. (MECz) was prepared and characterized by LC-ESI-MS/MS analysis. In vitro cytotoxicity and anti-proliferative activity of MECz was evaluated by MTT assay, while cell viability, apoptosis and cell cycle progression by Muse Cell analyzer. Furthermore, the mRNA and protein expressions of EMT markers were assessed using qRT-PCR and western blotting techniques, respectively. The MECz was found to be rich in phenolic compounds including chlorogenic acid, 6-gingerol, and certain triterpenes like ursolic acid etc. The apparent anti-metastasis activity of MECz was evident from IC50 value of 19.12 and 24.22μg/mL, respectively, on MDA-MB-231 and MCF-7 cells in MTT assay. An absolute decrease in cell viability (78.1-53.4% and 89.9-49.0%), augmented apoptosis (90.98-48.25% and 88.25-47.70%) and S phase, G2/M phase cell cycle arrest was found by MECz treatment on MDA-MB-231 and MCF-7 cells. The gene expression studies revealed that MECz could significantly (p < 0.001) regulate the expression of EMT markers such as snail, slug, zeb-1, twist-1, fibronectin, vimentin and E-cadherin at molecular level. These findings demonstrate that C. zeylanica L. root extract inhibits breast cancer cells growth and proliferation through regulating the expression of key EMT marker genes and proteins. Thus, MECz may be suggested as a potential anti-metastasis agent in the treatment of breast cancer.