Black Rice Anthocyanins Suppress Metastasis of Breast Cancer Cells by Targeting RAS/RAF/MAPK Pathway

• Published in: BioMed research international 2015-01, Vol.2015 (2015), p.1-11
• Main Authors: Yu, Xiao-Ping, Chen, Wei, Chen, Jing-Yao, Li, Fei, Han, Bin, Luo, Li-Ping, Zhou, Jie, Chen, Xiang-Yan, Zhu, Yan-Feng
• Format: Article
• Language: English
• Subjects: Anthocyanin; Anthocyanins - administration & dosage; Anthocyanins - chemistry; Breast cancer; Breast Neoplasms - drug therapy; Breast Neoplasms - genetics; Breast Neoplasms - pathology; Cancer cells; Cell adhesion & migration; Cell Line, Tumor; Cell Movement - genetics; Epidermal growth factor; Female; Gene Expression Regulation, Neoplastic - drug effects; Health aspects; Humans; Immunoglobulins; Kinases; MAP Kinase Kinase Kinase 1 - biosynthesis; MAP Kinase Kinase Kinase 1 - genetics; Matrix Metalloproteinase 2 - biosynthesis; Matrix Metalloproteinase 9 - biosynthesis; Metastasis; Mitogen-activated protein kinases; Neoplasm Invasiveness - genetics; Neoplasm Metastasis; Oryza - chemistry; Phosphorylation; Polyethylene terephthalate; Pore size; Prevention; Proteins; raf Kinases - biosynthesis; raf Kinases - genetics; ras Proteins - biosynthesis; ras Proteins - genetics; Receptor, ErbB-2 - genetics; Rice; Rodents; Signal Transduction - drug effects; Studies; Tumorigenesis
• ISSN: 2314-6133; 2314-6141
• DOI: 10.1155/2015/414250

Overexpression of human epidermal growth factor receptor 2 (HER2) drives the biology of 30% of breast cancer cases. As a transducer of HER2 signaling, RAS/RAF/MAPK pathway plays a pivotal role in the development of breast cancer. In this study, we examined the molecular mechanisms underlying the chemopreventive effects of black rice anthocyanins (BRACs) extract and identified their molecular targets in HER2+ breast cancer cells. Treatment of MDA-MB-453 cells (HER2+) with BRACs inhibited cell migration and invasion, suppressed the activation of mitogen-activated protein kinase kinase kinase (RAF), mitogen-activated protein kinase kinase (MEK), and c-Jun N-terminal kinase (JNK), and downregulated the secretion of matrix metalloproteinase 2 (MMP2) and MMP9. BRACs also weakened the interactions of HER2 with RAF, MEK, and JNK proteins, respectively, and decreased the mRNA expression of raf, mek, and jnk. Further, we found combined treatment with BRACs and RAF, MEK, or JNK inhibitors could enhance the antimetastatic activity, compared with that of each treatment. Transient transfection with small interfering RNAs (siRNAs) specific for raf, mek, and jnk inhibited their mRNA expression in MDA-MB-453 cells. Moreover, cotreatment with BRACs and siRNA induces a more remarkable inhibitory effect than that by either substance alone. In summary, our study suggested that BRACs suppress metastasis in breast cancer cells by targeting the RAS/RAF/MAPK pathway.