Abstract 1755: Prodigiosin inhibits the proliferation and migration of mcf-7 breast cancer cells through the demethylation of mir-200c gene

Abstract

Abstract Background: DNA methylation in microRNA (miRNA) host genes is associated with the down-regulation of gene expression in tumorigenesis and progression. Accumulating evidence shows that low levels of miR-200c were correlated with a worse prognosis in breast cancer. MiRNA promoter methylation has been reported as a major cause of miR-200c downregulation. Prodigiosin (PG), red bacterial pigment with a pyrrolylpyrromethene skeleton, has significant antibacterial, antifungal, antimalarial and antitumor activity via the modulation of multiple cell signaling pathways against a variety of human cancer cells. However, there is little information regarding the epigenetic-based effects of Prodigiosin in breast cancer. In this study, we hypothesize that Prodigiosin has anti-proliferative and anti-migration effects on breast cancer cells through the demethylation of miR-200c. Material and Methods: MCF-10A breast epithelial cells and MCF-7 breast cancer cells were used to investigate the effects of Prodigiosin on the expression and methylation of miR-200c using real time-PCR (RT-qPCR) and methylation-specific PCR (qMSP), respectively. MTS proliferation assay, cell scratch assay and three-dimensional (3D) formation assay were performed to assess the effect of Prodigiosin on the proliferation and migration of MCF-7 breast cancer cells. Result: MCF-7 breast cancer cells showed significant hypermethylation of miR-200c, and significantly down-regulated miR-200c expression compared to MCF-10A breast epithelial cells. Prodigiosin treatment led to significant inhibition of proliferation and migration, and significantly up-regulated miR-200c expression, whereas the methylation level of miR-200c significantly decreased in MCF-7 breast cancer cells. Conclusion: Prodigiosin, a secondary metabolite of bacteria, inhibits the proliferation and migration of breast cancer cells, and restores the demethylation status and expression of miR-200c. These findings elucidate that the demethylation of miR-200c may be a molecular mechanism underlying the anti-tumor of Prodigiosin in breast cancer. Citation Format: Fengqin Shi, Lingeng Lu, Peng LV, Ya Li, Hou Li, Xinyi Chen, Yong Zhu. Prodigiosin inhibits the proliferation and migration of mcf-7 breast cancer cells through the demethylation of mir-200c gene [abstract]. In: Proceedings of the Annual Meeting of the American Association for Cancer Research 2020; 2020 Apr 27-28 and Jun 22-24. Philadelphia (PA): AACR; Cancer Res 2020;80(16 Suppl):Abstract nr 1755.