Dietary flavonoid tangeretin induces reprogramming of epithelial to mesenchymal transition in prostate cancer cells by targeting the PI3K/Akt/mTOR signaling pathway

Tangeretin, a natural polymethoxyflavone present in the peel of citrus fruits is known to exhibit anticancer properties against a variety of carcinomas. Previous experimental evidence suggests that lifestyle and dietary habits affect the risk of prostate cancer to a certain extent. As the effect of tangeretin on prostate cancer is unexplored, the present study investigated the effect of tangeretin on androgen-insensitive PC-3 cells and androgen-sensitive LNCaP cells. Tangeretin reduced the cell viability of PC-3 cells in a dose- and time-dependent manner, with the half-maximal inhibitory concentration (IC50) observed at 75 mu M dose following 72 h of incubation, while in LNCaP cells, the IC50 was identified to be similar to 65 mu M. Expression levels of the mesenchymal proteins including vimentin, cluster of differentiation 44 and Neural cadherin in PC-3 cells were reduced by tangeretin treatment, whereas those of the epithelial proteins, including Epithelial cadherin and cytokeratin-19 were upregulated. Treatment of PC-3 cells also resulted in the downregulation of the phosphoinositide 3-kinase/protein kinase B/mammalian target of rapamycin (PI3K/Akt/mTOR) signaling pathway. Therefore, it may be concluded that tangeretin induces reprogramming of epithelial-mesenchymal transition in PC-3 cells by targeting the PI3K/Akt/mTOR signaling pathway.