Targeting Cyclin E by Phellinus Linteus for Colon Cancer Therapeutics

Purpose: Colon cancer is a common malignant disease with a high rate of cancer-related deaths. Current conventional chemotherapies to treat advanced colon cancer are not effective and often have serious side effects. Thus, there is an urgent need for discovering new treatments with a high efficacy and less toxicity. Because phellinus linteus (PL) has been widely used in Asia to treat cancers, we in this study investigated how the polysaccharides (P-PL) extracted from PL effectively targeted colon cancer cells. Methods: P-PL was used to test its effects on Human colon epithelial-like Caco-2 and cancerous HCT116 or HT29 cells IN VITRO and IN VIVO. The assays to analyze cell cycle progression, the expressions of G1/S cyclins and function of mRNA binding protein HuR were conducted for investigating the molecular mechanisms of the anti-colon cancer action of P-PL. Results: In this study, we demonstrated that P-PL treatment preferentially induced human colon cancer HCT116 or HT29 cells to apoptosis, but had a little cytotoxicity to the control, immortalized colon epithelial-like Caco-2 cells. P-PL-treated colon cancer cells accumulate in S phase of the cell cycle before underwent apoptosis. In this process, cyclin E (clnE) expression is decreased, which is due to the decrease of its mRNA stability. Furthermore, HuR function in treated cancer cells is perturbed. Conclusion: Taken together, our findings strongly suggest that P-PL is a potential anti-cancer medicine that can block malignant growth of colon cancer and has less cytotoxic side effects.