Transcriptional profiling of Chinese medicinal formula Si-Wu-Tang on breast cancer cells reveals phytoestrogenic activity

BMC Complementary and Alternative Medicine

Ying Huang⁴  Zhining Wen³  Leming Shi²  Moses SS Chow⁴  Zhong Zuo⁵  Charles Wang¹  Zhijun Wang⁴  Steven Wang⁴  Jeffery Fan⁴  Mandy Liu⁴ 

[1] Functional Genomics Core, Beckman Research Institute, City of Hope Comprehensive Cancer Center, Duarte, California;Department of Clinical Pharmacy and Center for Pharmacogenomics, School of Pharmacy, Fudan University, Shanghai, China;College of Chemistry, Sichuan University, Chengdu, Sichuan, China;Department of Pharmaceutical Sciences and Center for Advancement of Drug Research, College of Pharmacy, Western University of Health Sciences, Pomona, California;School of Pharmacy, Faculty of Medicine, The Chinese University of Hong Kong, Shatin, New Territories, Hong Kong, China

关键词: Transcriptional profiling;    Herbal medicines;    Breast cancer;    Chemoprevention;    Genomics;    Microarrays;    Phytoestrogens;   

Others  :  1231165
DOI  :  10.1186/1472-6882-13-11

 received in 2012-10-26, accepted in 2013-01-08,  发布年份 2013

【 摘 要 】

Background

Si-Wu-Tang (SWT), comprising the combination of four herbs, Paeoniae, Angelicae, Chuanxiong and Rehmanniae, is one of the most popular traditional oriental medicines for women’s diseases. In our previous study, the microarray gene expression profiles of SWT on breast cancer cell line MCF-7 were found similar to the effect of β-estradiol (E2) on MCF-7 cells in the Connectivity Map database.

Methods

Further data analysis was conducted to find the main similarities and differences between the effects of SWT and E2 on MCF-7 gene expression. The cell proliferation assay on MCF-7 (ER-positive) and MDA-MB-231 (ER-negative) cells were used to examine such estrogenic activity. The estrogenic potency of SWT was further confirmed by estrogen-responsive element (ERE) luciferase reporter assay in MCF-7 cells.

Results

Many estrogen regulated genes strongly up-regulated by E2 were similarly up-regulated by SWT, e.g., GREB1, PGR and EGR3. Of interest with regard to safety of SWT, the oncogenes MYBL1 and RET were strongly induced by E2 but not by SWT. Quantitative RT-PCR analysis revealed a highly concordant expression change in selected genes with data obtained by microarrays. Further supporting SWT’s estrogenic activity, in MCF-7 but not in MDA-MB-231 cells, SWT stimulated cell growth at lower concentrations (< 3.0 mg/ml), while at high concentrations, it inhibits the growth of both cell lines. The growth inhibitory potency of SWT was significantly higher in MDA-MB-231 than in MCF-7 cells. The SWT-induced cell growth of MCF-7 could be blocked by addition of the estrogen receptor antagonist tamoxifen. In addition, SWT was able to activate the ERE activity at lower concentrations. The herbal components Angelicae, Chuanxiong and Rehmanniae at lower concentrations (< 3.0 mg/ml) also showed growth-inducing and ERE-activating activity in MCF-7 cells.

Conclusions

These results revealed a new mechanism to support the clinical use of SWT for estrogen related diseases and possibly for cancer prevention. This study also demonstrated the feasibility of using microarray transcriptional profiling to discover phytoestrogenic components that are present in natural products.

【 授权许可】

   
2013 Liu et al.; licensee BioMed Central Ltd.

【 图 表 】

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