title: 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, the underlying molecular mechanisms are still not completely understood. In the current study, we investigated the effects of berberine on cell growth, colony formation, cell cycle distribution, and whether it improved the anticancer 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 significantly inhibited cell growth and colony formation in the two cell lines, berberine in combination with cisplatin exerting synergistic growth inhibitory effects. Accompanied by decreased growth, berberine induced G1 phase arrest in MCF-7 but not MDA-MB-231 cells. To provide a more detailed understanding of the mechanisms of action of berberine, 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 of the cell cycle, cell migration, apoptosis, and drug responses. To confirm the microarray data, qPCR analysis was conducted 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 mediated by alteration of gene expression profiles.
authors.affiliation: Institute of Life Sciences, Chongqing Medical University, Chongqing, China E-mail : hhzhou2003@163.com.
authors.forename: Chun-Jie
authors.initials: CJ
authors.lastname: Wen
authors.forename: Lan-Xiang
authors.initials: LX
authors.lastname: Wu
authors.forename: Li-Juan
authors.initials: LJ
authors.lastname: Fu
authors.forename: Jing
authors.initials: J
authors.lastname: Yu
authors.forename: Yi-Wen
authors.initials: YW
authors.lastname: Zhang
authors.forename: Xue
authors.initials: X
authors.lastname: Zhang
authors.forename: Hong-Hao
authors.initials: HH
authors.lastname: Zhou
mesh_terms: D000970:Antineoplastic Agents / Q000494:pharmacology*; D017209:Apoptosis; D001599:Berberine / Q000494:pharmacology*; D014408:Biomarkers, Tumor / Q000235:genetics*; D001943:Breast Neoplasms / Q000188:drug therapy* / Q000235:genetics; D002453:Cell Cycle; D049109:Cell Proliferation; D002945:Cisplatin / Q000494:pharmacology*; D004357:Drug Synergism; D005260:Female; D020869:Gene Expression Profiling; D023281:Genomics; D006801:Humans; D009363:Neoplasm Proteins / Q000235:genetics*; D020411:Oligonucleotide Array Sequence Analysis; D012333:RNA, Messenger / Q000235:genetics; D060888:Real-Time Polymerase Chain Reaction; D020133:Reverse Transcriptase Polymerase Chain Reaction; D014407:Tumor Cells, Cultured; D014410:Tumor Stem Cell Assay
chemical_list: D000970:Antineoplastic Agents; D014408:Biomarkers, Tumor; D009363:Neoplasm Proteins; D012333:RNA, Messenger; D001599:Berberine; D002945:Cisplatin