Long Non-coding RNAs Contribute to the Inhibition of Proliferation and EMT by Pterostilbene in Human Breast Cancer

There is increasing evidence that long non-coding RNAs (lncRNAs) are involved in the process of carcinogenesis and treatment using chemotherapy. Pterostilbene, a phytochemical agent with natural antioxidant and anti-inflammatory properties, has been shown to modulate oncogenic processes in many cancers. However, there has been limited research on the association between pterostilbene and the expression of lncRNAs. MCF7 breast cancer cells were treated with various concentrations of pterostilbene and their gene expression profile was analyzed by quantitative real-time PCR, Western blotting and immunofluorescence. Treatment with pterostilbene inhibited cell proliferation and epithelial-to-mesenchymal transition (EMT), and increased cell apoptosis, autophagy and ER stress. The Akt/mTOR pathway was downregulated, but p38 MAPK/Erk signaling was activated in cells following treatment with pterostilbene. Pterostilbene increased the expression of the lncRNAs MEG3, TUG1, H19, and DICER1-AS1 whereas the expression of LINC01121, PTTG3P, and HOTAIR declined. Knockdown of lncRNA H19 resulted in a reduction of the cell invasion, with the cells becoming more sensitive to pterostilbene therapy. These results suggest that efficient optimum disruption of lncRNA expression might possibly improve the anti-tumor effects of phytochemical agents, thus serving as a potential therapy for breast cancer.