Cancer Chemopreventive Activities of Silibinin on Colorectal Cancer through Regulation of E-Cadherin/β-Catenin Pathway
Saba Sameri, Massoud Saidijam, Fatemeh Bahreini, Rezvan Najafi
Abstract
PURPOSE: Silibinin is the most active flavonolignan constituent of Silymarin, the extract of milk thistle seeds. In this study, we investigated the anticancer properties and molecular mechanisms of silibinin on colorectal cancer (CRC) cells. METHODS: HCT-116 cells were used to investigate the effects of silibinin on proliferation, migration, epithelial-mesenchymal transition (EMT), cancer stem cells (CSCs), apoptosis and signaling pathways underlying these functions by using 3-(4,5-dimethylthiazol-2-yl)-2,5-diphenyltetrazolium bromide (MTT) and colony formation assay, quantitative reverse-transcription polymerase chain reaction (RT-qPCR), Western blot, Acridine orange/propidium iodide double staining, migration and sphere formation assay. RESULTS: Silibinin significantly suppressed HCT-116 cells proliferation and migration and induced the apoptosis via increasing the Bax/Bcl-2 ratio. Silibinin down-regulated cancer stemness markers; prominin-1 (CD133), CD44, BMI1, Aldehyde dehydrogenase 1 (ALDH1), and doublecortin-like kinase 1 (DCLK1) of HCT-116 cell line. Silibinin attenuated EMT through decreased expression of N- cadherin and vimentin and increased expression of (E-cadherin). Furthermore, silibinin decreased the β-catenin gene and protein expression. CONCLUSION: Our study revealed that silibinin maintains various antitumor activities such as induction of apoptosis, suppression of migration, elimination of CSCs and attenuation of EMT related markers in CRC cells. These underlying anti-tumor mechanisms of silibinin are likely to act through the blockage of the β-catenin signaling pathway, which is the key component of Wnt signaling pathway, one of the hallmarks of CRC development.