Tricin inhibits the migration of human retinal pigment epithelium cells by suppressing the RUNX2-CYP1A1 axis and STAT3 pathway

Proliferative vitreoretinopathy (PVR) is a retinal disorder characterized by abnormal growth and migration of retinal pigment epithelium (RPE) cells, leading to impaired visual acuity. Tricin is a naturally occurring flavone known to inhibit the migration of various cancer cell types. Therefore, the aim of this study was to investigate the potential inhibitory effects of tricin on the migration of ARPE-19 cells. In this study, tricin treatment significantly reduced the migratory and invasive abilities of ARPE-19 cells in the Boyden chamber assays. RNA sequencing identified cytochrome P450 1A1 (CYP1A1) as the most significantly downregulated gene following tricin treatment. Real-time PCR confirmed a reduction in CYP1A1 mRNA levels, while Western blot analysis demonstrated a concentration-dependent decrease in CYP1A1 protein expression. Moreover, siRNA-mediated knockdown of CYP1A1 resulted in decreased mRNA expression levels, accompanied by reduced cell migration. Tricin treatment also attenuated RUNX2 transcription factor levels and phosphorylation of STAT3. Co-treatment with tricin and colivelin (a STAT3 activator) led to increased CYP1A1 expression and enhanced cell migration, suggesting a regulatory role of the STAT3 pathway in tricin-mediated effects. In conclusion, tricin inhibits the migration of ARPE-19 cells by downregulating CYP1A1 and RUNX2 expression through suppression of the STAT3 signaling pathway. These findings suggest that tricin holds potential as a therapeutic candidate for preventing or limiting the progression of PVR.