Berberine Reverses the Tumorigenic Function of Colon Cancer Cell-Derived Exosomes

Abstract

Exosomes derived from colon cancer cells has been found to elevate viability and metastasis of recipient cells. Berberine is a plant-derived natural compound that has shown anti-colon cancer potential. However, berberine’s impacts on the tumorigenic functions of tumor exosomes have yet to be evaluated. To elucidate whether berberine modulates exosomal pro-tumor activity, we evaluated the effects of exosomes released by berberine-treated colon cancer cells against viability, migration, and invasion of recipient cancer cells. The human colon cancer HCT116 cells were treated or not treated with berberine, and culture media were collected following 48 h of treatment. Exosomes released by treated or untreated cells were isolated from collected media via ultracentrifugation. To study effects of berberine on tumor exosomes, HCT116 cells were co-cultured with exosomes derived from berberine-treated and non-treated cells, followed by monitoring changes in cell viability, migration, and invasion. The treatment with 100, 150, and 200 µg/ml of berberine-primed exosomes could dose-dependently decrease the viability [by −35.4% (p < 0.0001), −47% (p < 0.0001), and −65.5% (p < 0.0001), respectively], migration [by −24% (p = 0.0001), −43.5% (p = 0.0001), and −65.2% (p = 0.0001), respectively], and invasion [by −29% (p < 0.0001), −58.8% (p < 0.0001), and −69.7% (p < 0.0001), respectively] of HCT116 cells compared to the control. However, non-primed exosomes exerted significant inducing effects on the viability and metastatic ability of HCT116 cells. In conclusion, berberine can reverse the tumorigenic function of colon cancer exosomes and, thus, exert a remarkable suppressive impact against the survival and metastatic ability of colon cancer cells.