Evening primrose seed extract rich in polyphenols modulates the invasiveness of colon cancer cells by regulating the TYMS expression

Abstract

Natural polyphenols are plant metabolites exhibiting a broad range of biological activities. Among them, anticancer properties seem to be very desirable. This study examined the anticancer and anti-metastatic properties of the polyphenol-rich extract from the evening primrose seeds (EPE). In vitro and in vivo studies performed in colorectal cancer (CRC) cell lines and AOM-DSS-induced colitis-associated colon cancer in mice revealed the EPE anticancer properties. Furthermore, we studied the EPE activity on metastatic abilities and showed that the EPE inhibited invasiveness in the following models (cells isolated from patients with different invasive stages and cells with induced invasion by either Snail overexpression or CAF stimulation). More importantly, we also demonstrated that the EPE decreases the cell invasiveness of 5-fluorouracil (5-FU) resistant CRC cells. The inhibition of metastasis correlated with a decrease in thymidylate synthetase (TYMS), which has recently been associated with metastatic phenotype development. Our results indicate that the EPE might be an effective anticancer agent in suppressing colon cancer metastasis regardless of the invasiveness cause. Based on these findings, we concluded that the used EPE extract rich in polyphenols inhibits cell invasion by TYMS downregulation.