Berberine Decreases Cell Growth but Increases the Side Population Fraction of H460 Lung Cancer Cells

Berberine has been reported to inhibit tumor growth in lung cancer. Thus, the effects of berberine on cancer cells as well as the cancer stem cell (side population; SP) fraction were investigated in the H460 lung cancer cell line, and the effects of berberine treatment on cell growth, cell cycle, and cell death were evaluated. Changes in the SP fraction were examined after treatment with berberine, 5-fluorouracil (5-FU), and co-treatment. Berberine inhibited cancer cell growth in a dose-dependent manner. Treatment of the cells with berberine resulted in a 4% increase in cell death and an 8% increase in the number of cells of G∧0/G₁ phase, compared to the untreated control. To examine the relationship between berberine and cancer stem cells, the SP fraction was analyzed. Surprisingly, the SP cell fraction was increased upon berberine treatment and further increased after cotreatment with 5-FU. These results are in contrast to the study of Kim et al. (2008) with MCF-7 breast cancer cells, in which berberine inhibited the growth of both cancer cells and the corresponding cancer stem cells. Results of the present study suggest that berberine should be used with caution in the treatment of various cancers, despite its positive effect on cancer cell growth inhibition.