Polyphenolic Extract from Mangifera indica is Cytotoxic in ER + BT474 Breast Cancer Cells and Targets the SHIP‐1‐Phosphatidylinositol3‐kinase (PI3K)‐Akt through microRNA‐155

Abstract

The objective of this research was to understand the post‐transcriptional targets involved in anti‐inflammatory and pro‐apoptotic pathways in estrogen receptor positive (ER+) breast cancer cells BT474 treated with a polyphenolic extract (2.5–40μg/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. NF‐kB protein and mRNA expression as well as activation were decreased in a dose‐dependent manner accompanied by increased expression of IKKα/β kinases, and impaired IκB degradation.The extract also inhibited PI3K dependent phosphorylation of AKT and increased in SHIP‐1 expression and this was accompanied by down‐regulation of miRNA 155 of BT474 (0.6 fold) and in vivo. Results were confirmed by using a mimic for miR‐155 which in part reversed the effects of the extracts. NFκB‐dependent genes involved in anti‐apoptosis, metastasis and angiogenesis, such as survivin, VCAM‐1, and VEGF were also decreased.In summary the anti‐carcinogenic and anti‐inflammatory activity of mango polyphenolics in breast cancer cells were at least in part due to targeting miR‐155‐SHIP‐1‐Phosphatidylinositol 3‐kinase (PI3K)‐Akt‐NF‐kB which plays an important role in the proliferative/inflammatory phenotype exhibited in this breast cancer cell line.Grant Funding Source : NIH