Genomic Screening for Targets Regulated by Berberine in Breast Cancer Cells

Abstract

Berberine, a common isoquinoline alkaloid, has been shown to possess anti-cancer activities. However, theunderlying molecular mechanisms are still not completely understood. In the current study, we investigatedthe effects of berberine on cell growth, colony formation, cell cycle distribution, and whether it improved theanticancer efficiency of cisplatin and doxorubicin in human breast cancer estrogen receptor positive (ER+)MCF-7 cells and estrogen receptor negative (ER-) MDA-MB-231 cells. Notably, berberine treatment significantlyinhibited cell growth and colony formation in the two cell lines, berberine in combination with cisplatin exertingsynergistic growth inhibitory effects. Accompanied by decreased growth, berberine induced G1 phase arrest inMCF-7 but not MDA-MB-231 cells. To provide a more detailed understanding of the mechanisms of action ofberberine, we performed genome-wide expression profiling of berberine-treated cells using cDNA microarrays.This revealed that there were 3,397 and 2,706 genes regulated by berberine in MCF-7 and MDA-MB-231 cells,respectively. Fene oncology (GO) analysis identified that many of the target genes were involved in regulation ofthe cell cycle, cell migration, apoptosis, and drug responses. To confirm the microarray data, qPCR analysis wasconducted for 10 selected genes based on previously reported associations with breast cancer and GO analysis.In conclusion, berberine exhibits inhibitory effects on breast cancer cells proliferation, which is likely mediatedby alteration of gene expression profiles.