Plant phenolics as chemopreventive agents of colorectal cancer

The progression of colorectal neoplasia from adenoma to carcinoma results from a step-wise accumulation of several mutations in genes responsible for molecular components that induce cell proliferation through the upregulation of the PI3K/Akt and MAPK/ERK pathways and/or downregulation of the apoptosis pathways. Other important players are cyclooxygenase 2 (COX-2), nuclear factor Kappa B (NF-kB), survivin, and insulin-like growth factor-I (IGF-I). Together, they constitute potential targets for CRC prevention. In this work, an overview of some of the most promising plant phenolics as inhibitors of colorectal tumorigenesis will be presented, emphasizing the results of preclinical or clinical trials and discussing the respective action mechanisms. Two human CRC cell lines harboring mutations in different genes coding for different components of the PI3K/Akt and MAPK/ERK pathways were used, in order to evaluate the potential CRC prevention of Salvia and Hypericum phenolic extracts and some of their constituents. The results showed that both extracts and components regulated differently the expression of key components of PI3K/Akt and MAPK/ERK pathways and apoptosis pathways depending of mutated gene harbored by the target cell line. In conclusion, the CRC prevention efficacy depends from the kind of respective target component and the kind of the CRC mutated genes.