Polyphenols from mango (Mangifera indica L.) modulate PI3K/AKT/mTOR-associated micro-RNAs and reduce inflammation in non-cancer and induce cell death in breast cancer cells

Dietary polyphenols are known to exert health benefits through modulation of signaling networks. This study investigated the modulation of micro-RNAs associated with the PI3K/AKT/mTOR-axis by mango polyphenols (MP) in MCF-12A non-cancer and MDA-MB231 breast cancer cell lines. MP reduced proliferation in the cancer cells by up to 90% (10 mg GAE/L) but did not cause cytotoxicity in the non-cancer cells within the same concentration range. In contrast, in TNF-alpha-treated non-cancer MCF-12A cells, MP significantly decreased expression and phosphorylation of NF-kappa B while modulating mRNA and protein levels of PI3K/AKT/mTOR and up-regulated miR-126. The mechanistic involvement of miR-126 was investigated using its antagomiR. In MDA-MB231 cells, miR-126 was not affected. However, polyphenols modulated the PI3K/AKT/mTOR-axis and down-regulated miR-21 while the expressions of NF-kappa B and biomarkers for inhibition of apoptosis, namely, PARP-1 and Bcl-2 decreased. Overall, MP reduced inflammation in non-cancer and proliferation in breast cancer cells by differentially modulating PI3K/AKT/mTOR and associated micro-RNAs.