Effects of pomegranate seed extract and ellagic acid on miR-16-5p and miR-34a-5p expression, cell cycle, and apoptosis in MCF-7 cells

Background and purpose: The expression of Homo sapiens (has)-miR-16-5p and hsa-miR-34a-5p with anti-tumor effects is downregulated in cancer cells. To maintain these gene expressions in cancer cells, we evaluated the effects of pomegranate seed extract (PSE) and ellagic acid (EA) on hsa-miR-16-5p and hsa-miR- 34a-5p expression, cell cycle regulation, and apoptotic induction in the MCF-7 cells encapsulated in the alginate hydrogel, a 3D culture system. Experimental approach: MCF-7 cells were encapsulated in 3-D alginate scaffolds and cultured (experimental groups: EA, PSE, EA and PSE, and the control group). Cell viability (using MTT assay), cell apoptosis (via flow cytometry), the level of malondialdehyde (MDA), and the expression levels of hsa-miR-16-5p, hsa-miR- 34a-5p, B-cell lymphoma 2 (BCL-2), cyclin D1 (CCND1), and sirtuin 1 (SIRT1) were measured (via real-time PCR). Findings/Results: The combination of PSE and EA exhibited the greatest effects on MCF-7 cells. EA and PSE increased the expression of hsa-miR-16-5p and hsa-miR-34a-5p and decreased the expression of the SIRT1 and CCND1 genes. In addition, the antiapoptotic BCL-2 gene was downregulated in the experimental group. Both antioxidants significantly increased the population of MCF-7 cells in the G1 phase. Additionally, antioxidants reduce the level of MDA in cancer cells. Conclusion and implications: EA and PSE antioxidants increased hsa-miR-16-5p and hsa-miR-34a-5p expression, induced apoptosis, decreased cell proliferation, and stopped cancer cells in the G1 phase. Therefore, they can be considered promising compounds for helping the treatment of breast cancer.