Up-regulation of multidrug resistance transporter expression by berberine in human and murine hepatoma cells.

Berberine, one of the major constitutents of alkaloids of Coptis chinensis is frequently utilized in the treatment of inflammation and liver-related diseases. In Chinese herbal medicine, Coptis chinensis is used as a prophylactic drug to treat gastrointestinal disorders. In a previous study, the authors found that berberine reduced cell proliferation and alpha-fetoprotein expression in human hepatoma HepG2 cells. Multidrug resistance transporter (pgp-170) is known to be overexpressed in HepG2 cells. Whether berberine regulates the expression of pgp-170 in HepG2 and other hepatoma cell lines is unknown and worthy of investigation. Human and murine hepatoma cells were treated with berberine (0.32, 3.2, 32, and 320 microM), tamoxifen (1 microM), or verapamil (10 microM) for 24 hours. Flow cytometry was used to measure retention of a fluorescence dye, rhodamine 123, and the level of immunoreactive pgp-170 in berberine-treated hepatoma cells. Berberine up-regulated the expression of pgp-170 in three human hepatoma cell lines. The function of pgp-170 was blocked by tamoxifen and verapamil, resulting in increased retention of rhodamine 123. Retention of rhodamine 123 was significantly reduced in berberine-treated hepatoma cells. Berberine modulates the expression and function of pgp-170 in hepatoma cells. These results suggest that treatment of tumor cells with berberine may result in reduced retention of chemotherapeutic agents.