The Combined Impact of Curcumin: Piperine and Sorafenib on microRNAs and Different Pathways in Breast Cancer Cells

Breast cancer is the most common malignancy in the women. Chemotherapy is a crucial part of breast cancer treatment especially for advanced and metastatic forms of the disease. However, chemotherapy has limitations due to tumor heterogeneity, chemoresistance, and side effects. There is potential in combining chemotherapeutic drugs with natural items to enhance their effectiveness against cancer. In this study, we examined the synergistic effects of combining curcumin: piperine with sorafenib on the progression of breast cancer cells by altering many pathways associated with cancer and regulating the expression of numerous microRNAs. We tested the cytotoxic impact of curcumin: piperine on MCF-7 breast cancer cells using SRB assay. We analyzed the expression levels of selected microRNAs, genes, and proteins related to cancer stem cells, epithelial-mesenchymal transition, apoptosis and cell cycle progression using qPCR, ELISA and flow cytometry techniques. The findings of this study demonstrated that sorafenib and curcumin: piperine together enhances the suppression of MCF-7 cell survival. Molecular genetic analysis revealed that this combination provoked downregulation in oncomirs [miR-21 and miR-155], vimentin, Snail1, Notch, TGF-β1, Smad4, β-catenin1 and Wnt10b genes. Meanwhile, there were upregulation of tumor suppressor miRNAs [miR-28, miR-139 and miR-149] and E-cadherin gene expression level. Also, this combination resulted in a decrease of vimentin, IL-6, STAT3 and MMP-9; an increase of E-cadherin protein levels. Moreover, this combination induced apoptotic cell death and arrested cell cycles at specific phases. This study suggests that the combination of sorafenib and curcumin: piperine can combat breast cancer by modulating several microRNAs and signaling pathways involved in the development and progression of breast cancer.