Chlorogenic acid regulates the proliferation and migration of high-grade serous ovarian cancer cells through modulating the miR199a5p/DDR1 axis.

Abstract

This study aimed to demonstrate that chlorogenic acid (CGA) has anticancer effects against ovarian cancer. The MTT assay was used to assess the optimum concentrations of CGA on the ovarian cancer cell lines OVCA433 and SKOV3, followed by the rate of apoptosis using Annexin V-FITC/PI. The mitochondrial membrane potential of ovarian tumour cells treated with CGA was evaluated using mitochondrial staining kits followed by Western blot analysis, immunofluorescence, and RT-PCR assays. The Trans-well migration assay conducted the percentage of cell migration, followed by wound healing and colony formation assays. CGA induces activation of mitochondria-mediated intrinsic apoptotic pathways in ovarian cancer cells. The discovery that miR-199a-5p is inversely correlated to DDR1, a receptor tyrosine kinase involved in collagen synthesis, was the major consequence of examining the various mechanisms involved in the development of ovarian cancer. After treatment with CGA, cells derived from ovarian cancer cells were deregulated partially via the miR199a5p/DDR1 axis, significantly affecting tumour suppression. DDR1 has been identified as a direct target of miR199a5p in these ovarian cancer cells. We found that CGA-induced loss of DDR1 caused the inactivation of NF-κB signalling downstream in the MMP, migration, and EMT pathways. The study results showed that CGA is a promising drug candidate for treating ovarian cancer, particularly because it exhibits anti-invasive and migrastatic properties.