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.
Sadeghi et al. (Fri,) studied this question.