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.

A gene expression signature-based approach reveals the mechanisms of action of the Chinese herbal medicine berberine

“…Although BBR is regarded as a potential therapeutic drug for breast cancer, a better understanding of genes and cellular pathways regulated by BBR is needed to define the mechanisms of its action in cancer treatment39. A recent study also performed genome-wide expression profiling of BBR-treated human breast cancer cells (MCF-7 and MDA-MB-231 cells) using complementary DNA (cDNA) microarrays40. This study identified that many of the target genes of BBR are involved in regulating the cell cycle and cell migration40, which is comparable to our findings.…”

The antioxidant and chemical properties of Berberis vulgaris and its cytotoxic effect on human breast carcinoma cells

“…Berberis vulgaris is one of these medicinal plants that have various biological properties including anti-proliferative, antimigratory and antioxidant activities (Mahata et al 2011;Wen et al 2013). Previous studies mentioned that the phytochemical constituents of Berberis such as antioxidants and anthocyanins increased its bioactivity and was affected by different extraction procedures or the type of solvents used (Abd Elwahab et al 2013;Annegowda et al 2011).…”

“…The medicinal properties for all parts of this plant have been reported including antimicrobial, antiemetic, antioxidant and anticancer activities (Wen et al 2013;Končić et al 2010;Abd El-wahab et al 2013). The aim of the present study was to examine and compare the biological in vitro activities (antioxidant, anticancer and apoptotic properties) of alcoholic and aqueous extracts of Berberis fruits in human breast cancer cells, MCF-7 in comparison with the normal human epithelial cells (MCF10-A).…”

“…So, it is required to apply effective therapies without side effects. In this context, the use of natural components such as herbs may find a new safe way for breast cancer treatment (Wen et al 2013;Shafi Sofi et al 2013;Fathi Najafi et al 2007).…”

Berberine Hydrochloride Impact on Physiological Processes and Modulation of Twist Levels in Nasopharyngeal Carcinoma CNE-1 Cells

“…Cai-Hong Li 1,2 , Dong-Fang Wu 1 , Hang Ding 2 , Yang Zhao 3 , Ke-Yuan Zhou 2 *, De-Feng Xu 4 * proliferation of various cancer types via the induction of cell cycle arrest and cellular apoptosis (Mantena et al, 2006;Lin et al, 2007;Kuo et al, 2011;Wen et al, 2013). Furthermore, the application of BH has attracted considerable attention for its use as an anti-metastatic agent, suggesting its use in a variety of advanced cancers (Kim et al, 2008;Ho et al, 2009;Kim et al, 2011;Singh et al, 2011).…”