Epithelial-mesenchymal transition (EMT) is considered as the most important mechanism that underlies the initiation of
cancer metastasis. Here we report that the naturally existing
flavonoid,
hispidulin is capable of preventing human
colorectal cancer cells from
hypoxia-induced EMT. The treatment of the cells with
hispidulin reversed the EMT-related phenotype that has the morphological changes, down-regulation of
E-cadherin, and
hypoxia-induced cell migration and invasion. The effect was mediated at least in part by inhibiting the
mRNA and
protein expressions of HIF-1α via modulation of PTEN/PI3K/Akt pathway. In addition, we found that
hispidulin-mediated prevention of the
E-cadherin down-regulation and cell motility involved blockade of the
hypoxia-induced up-regulation of Snail, Slug and Twist.
Hispidulin was also effective in increasing expression of
E-cadherin mRNA in HT29
colorectal cancer xenografts implanted in the nude mice. In summary, this study showed that
hispidulin can prevent EMT induced by
hypoxia, the environment that commonly exists in the center of a solid
tumor. Given the low toxicity of
hispidulin to the healthy tissues, our study suggests that
hispidulin can serve as a safe therapeutic agent for suppressing
cancer metastasis.