Ellagic acid suppresses the human renal carcinoma cell migration and invasion by targeting the RUNX2/MMP1 expression

Ellagic acid (EA) exerts anti-carcinogenic activity in various types of cancer. Matrix metalloproteinases (MMPs) are critical mediators in the pathogenesis of renal cell carcinoma (RCC) metastasis. Using in vitro experiments, this study aims to investigate the mechanisms by which EA inhibits RCC migration and invasion. The findings show that EA treatment inhibited RCC cell migration and invasion without reducing cell viability in normal human kidney cells (HK2 cells) and RCC cells (786-O and ACHN). A human proteinase array showed that EA treatment decreased MMP1 mRNA and protein expression levels in 786-O and ACHN cell lines. MMP1 expression is elevated in RCC tissues and correlates with tumor grade, stage, and overall survival in RCC patients. Our molecular docking model indicates a strong interaction between EA and MMP1. The addition of recombinant human MMP1 (Rh-MMP1) to RCC cells increased their migration and invasion; co-treatment with Rh-MMP1 and EA effectively reversed these effects. EA reduced the expression of the transcription factor RUNX2 in both RCC cell lines and knockdown of RUNX2 significantly decreased the migration and invasion abilities of EA-treated 786-O cells. High expression of RUNX2 in RCC patients is associated with higher tumor grade, stage, and poorer survival and correlates positively with MMP1 expression level. These results suggest that EA suppresses RUNX2 targeting of MMP1 expression, thereby conferring anti-invasive properties on RCC cells.