title: Black Rice Anthocyanins Suppress Metastasis of Breast Cancer Cells by Targeting RAS/RAF/MAPK Pathway.
abstract: 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.
authors.affiliation: Department of Public Health, Chengdu Medical College, Chengdu 610500, China.
authors.forename: Xiang-Yan
authors.initials: XY
authors.lastname: Chen
authors.affiliation: Department of Public Health, Chengdu Medical College, Chengdu 610500, China.
authors.forename: Jie
authors.initials: J
authors.lastname: Zhou
authors.affiliation: Department of Public Health, Chengdu Medical College, Chengdu 610500, China.
authors.forename: Li-Ping
authors.initials: LP
authors.lastname: Luo
authors.affiliation: Department of Public Health, Chengdu Medical College, Chengdu 610500, China.
authors.forename: Bin
authors.initials: B
authors.lastname: Han
authors.affiliation: Department of Public Health, Chengdu Medical College, Chengdu 610500, China.
authors.forename: Fei
authors.initials: F
authors.lastname: Li
authors.affiliation: Department of Public Health, Chengdu Medical College, Chengdu 610500, China.
authors.forename: Jing-Yao
authors.initials: JY
authors.lastname: Chen
authors.affiliation: Department of Public Health, Chengdu Medical College, Chengdu 610500, China.
authors.forename: Yan-Feng
authors.initials: YF
authors.lastname: Zhu
authors.affiliation: Department of Public Health, Chengdu Medical College, Chengdu 610500, China.
authors.forename: Wei
authors.initials: W
authors.lastname: Chen
authors.affiliation: Department of Public Health, Chengdu Medical College, Chengdu 610500, China.
authors.forename: Xiao-Ping
authors.initials: XP
authors.lastname: Yu
mesh_terms: D000872:Anthocyanins / Q000008:administration & dosage* / Q000737:chemistry; D001943:Breast Neoplasms / Q000188:drug therapy* / Q000235:genetics / Q000473:pathology; D045744:Cell Line, Tumor; D002465:Cell Movement / Q000235:genetics; D005260:Female; D015972:Gene Expression Regulation, Neoplastic / Q000187:drug effects; D006801:Humans; D048728:MAP Kinase Kinase Kinase 1 / Q000096:biosynthesis* / Q000235:genetics; D020778:Matrix Metalloproteinase 2 / Q000096:biosynthesis; D020780:Matrix Metalloproteinase 9 / Q000096:biosynthesis; D009361:Neoplasm Invasiveness / Q000235:genetics; D009362:Neoplasm Metastasis; D012275:Oryza / Q000737:chemistry; D018719:Erb-b2 Receptor Tyrosine Kinases / Q000235:genetics; D015398:Signal Transduction / Q000187:drug effects; D048490:raf Kinases / Q000096:biosynthesis* / Q000235:genetics; D018631:ras Proteins / Q000096:biosynthesis* / Q000235:genetics
chemical_list: D000872:Anthocyanins; D048728:MAP Kinase Kinase Kinase 1; D020778:Matrix Metalloproteinase 2; D020780:Matrix Metalloproteinase 9; D018719:Erb-b2 Receptor Tyrosine Kinases; D048490:raf Kinases; D018631:ras Proteins; C508053:ERBB2 protein, human