Gallic acid inhibit MCF۷ breast cancer cell Proliferation by CCR۵ targeting

Introduction: Gallic acid, a plant‑derived natural agent, has potential effects to prevent of progression and development of various cancers including breast cancer. The CC-chemokine receptor ۵ (CCR۵) is a cell surface receptor that has a strong affinity for chemotropic cytokines. CCR۵ was up-regulated in different type of cancers and has gained attention as therapeutic target in various malignancies and solid tumors. Therefore, the aim of the present study was the evaluation gallic acid effect on cell growth and CCR۵ expression as a therapeutic agent. Methods: MCF۷ breast cancer cells cultured in DMEM containing ۱۰% FBS, ۱۰۰ U/ml penicillin/ streptomycin at ۳۷°C with ۵% CO۲. Cells treated with different concentration of gallic acid and then cell proliferation in treated cells vs. control were estimated by the MTT assay. For gene expression of CCR۵, microarray data in gallic acid treatment analyzed and fold change evaluated. Results: MTT assays showed that cell proliferation in the MCF-۷ cells treated with gallic acid considerably inhibited. Furthermore, the microarray data analysis indicates that gallic acid down-regulated the expression of CCR۵ gene in breast cancer cells. Future analysis revealed that the down-regulation of CCR۵ correlate with the DNA-damaging and inhibition of stemness and migratory phenotype. Conclusion: Our results suggest that gallic acid may engagement at least part of its anticancer effect by down-regulation of CCR۵. In addition to CCR۵ stimulates oncogenic pathways, DNA repair and upregulation of antiapoptotic genes, therefore targeting CCR۵ by natural agent has the possibility to suppress proliferation in cancer.