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Asian Pacific Journal of Cancer Prevention, Vol 15, 2014 6219DOI:http://dx.doi.org/10.7314/APJCP.2014.15.15.6219Anthocyanin Inhibitory Effects in ErbB2 Positive Breast Cancer Cells and a Tumoral Xenograft ModelAsian Pac J Cancer Prev, 15 (15), 6219-6225IntroductionBreast cancer is now the most frequently diagnosed malignancy and the leading global cause of cancer motility in women, accounting for 23% of cancer diagnoses (1.38 million) and 14% of cancer deaths (458 000) each year (DeSantis et al., 2011; Jemal et al., 2011). The decrease in breast cancer-related deaths has been observed in the developed world since the early 1990s, partly due to improved screening and adjuvant treatment (Berry et al., 2005). Despite the advances that have been made in the treatment of breast cancer, metastasis remains the leading cause of breast cancer mortality (Siegel et al., 2012; Gretel et al., 2013).Human epidermal growth factor receptor-2 (HER2/neu, ErbB2) is a family member of epidermal growth factor receptor (EGFR) membrane tyrosine kinase and plays an important role in cell proliferation, differentiation and migration (Gutierrez et al., 2011). Prior researches have revealed that breast cancer progression and poor prognosis are always positively correlated with ErbB2 amplification and resultant ErbB2 protein overexpression (Nahta et al., 2009; Bernasconi et al., 2012; Olson et al., 1 Department of Public Health, Chengdu Medical College, 2 School of Life Science and Engineering, Southwest Jiaotong University, Chengdu, China & Equal contributors *For correspondence: cyggwsyxp@sina.comAbstract Background: Increasing evidence from animal, epidemiological and clinical investigations suggest that dietary anthocyanins have potential to prevent chronic diseases, including cancers. It is also noteworthy that human epidermal growth factor receptor 2 (ErbB2) protein overexpression or ErbB2 gene amplification has been included as an indicator for metastasis and higher risk of recurrence for breast cancer. Materials and Methods: The present experiments investigated the anti-metastasis effects of black rice anthocyanins (BRACs) on ErbB2 positive breast cancer cells in vivo and in vitro. Results: Oral administration of BRACs (150 mg/kg/day) reduced transplanted tumor growth, inhibited pulmonary metastasis, and decreased lung tumor nodules in BALB/c nude mice bearing ErbB2 positive breast cancer cell MDA-MB-453 xenografts. The capacity for migration, adhesion, motility and invasion was also inhibited by BRACs in MDA-MB-453 cells in a concentration dependent manner, accompanied by decreased activity of a transfer promoting factor, urokinase-type plasminogen activator (u-PA). Conclusions: Together, our results indicated that BRACs possess anti-metastasis potential against ErbB2 positive human breast cancer cells in vivo and in vitro through inhibition of metastasis promoting molecules. Keywords: Breast cancer - anthocyanins - metastasis - tumor models - black riceRESEARCH ARTICLEAnti-metastasis Activity of Black Rice Anthocyanins Against Breast Cancer: Analyses Using an ErbB2 Positive Breast Cancer Cell Line and Tumoral Xenograft ModelLi-Ping Luo 1,2& , Bin Han 1& , Xiao-Ping Yu 1 *, Xiang-Yan Chen 1 , Jie Zhou 1 , Wei Chen 1 , Yan-Feng Zhu 1 , Xiao-Li Peng 1 and Qiang Zou 1 , Sui-Yan Li 22013). While ErbB2 lacks an identified ligand, ErbB2 kinase activity can be activated in the absence of a ligand when overexpressed and/or through heteromeric associations with other ErbB family members (EGFR, ErbB3 and ErbB4) (Zhang et al., 2007; Aertgeerts et al., 2011). Previous studies reported that 47% (344 of 733) amplification of the ErbB2 gene and 35% (279 of 798) overexpression of its product are detected in human breast cancers by FISH (fluorescence chromosomal in situ hybridization) and IHC (immunohistochemistry), respectively (Press et al., 2008).Anthocyanins are found in foods of vegetable, fruit and cereal origin. Flavonoids, including anthocyanins, have attracted much attention for the potential health benefits in obesity control (Prior et al., 2008), diabetes control (Wedick et al., 2012), cardiovascular disease (CVD) prevention (Van et al., 2013), visual (Shim et al., 2012) and brain function (Gutierres et al., 2012) improvement, mainly due to its anti-inflammatory, antioxidant and chemoprotective properties (Wang et al., 2007; Stoner et al., 2011; Tsuda, 2012). In recent years, scientists newly found that anthocyanins can prevent carcinogenesis, and inhibit cancer progress and metastasis through cell signal