Author(s): Suthakar Ganapathy, Tianqi Yu, Ling Shen, Bo Peng, Sung-Hoon Kim and Changyan ChenPurpose: 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.