Polyphenolic Extract from Mangifera indica is Cytotoxic in ER + BT474 Breast Cancer Cells and Targets the SHIP1Phosphatidylinositol3kinase (PI3K)Akt through microRNA155
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The objective of this research was to understand the posttranscriptional targets involved in antiinflammatory and proapoptotic pathways in estrogen receptor positive (ER+) breast cancer cells BT474 treated with a polyphenolic extract (2.540g/ml) rich in gallotannins and galic acid from Mangifera Indica L in vitro and in nude mice with BT474 cells as xenografts. Results show that cell proliferation as well as tumor size and weight in vivo was decreased by polyphenolics. NFkB protein and mRNA expression as well as activation were decreased in a dosedependent manner accompanied by increased expression of IKK/ kinases, and impaired IB degradation.The extract also inhibited PI3K dependent phosphorylation of AKT and increased in SHIP1 expression and this was accompanied by downregulation of miRNA 155 of BT474 (0.6 fold) and in vivo. Results were confirmed by using a mimic for miR155 which in part reversed the effects of the extracts. NFBdependent genes involved in antiapoptosis, metastasis and angiogenesis, such as survivin, VCAM1, and VEGF were also decreased.In summary the anticarcinogenic and antiinflammatory activity of mango polyphenolics in breast cancer cells were at least in part due to targeting miR155SHIP1Phosphatidylinositol 3kinase (PI3K)AktNFkB which plays an important role in the proliferative/inflammatory phenotype exhibited in this breast cancer cell line.Grant Funding Source: NIH
