Dose matters: Direct killing or immunoregulatory effects of natural polysaccharides in cancer treatment.

Polysaccharides from natural resources possess anti-tumor activities for decades, but the efficacy of polysaccharides as the adjuvant drugs for cancer treatment at prescribed doses remains open for debate. In this review, molecular mechanisms involved in direct killing effects of polysaccharides, including apoptosis, cell cycle arrest and mitochondria/DNA damage were described. However, the concentrations/doses used to reach the direct killing effects are too high to be applicable. Polysaccharides can also exert anti-tumor effects through immunoregulation at lower doses, and the effects of polysaccharides on natural killer cells, dendritic cells and other lymphocytes for tumor destruction, along with the receptor recognition and downstream signaling pathways, were delineated. Unfortunately, the prescribed doses of polysaccharides are too low to stimulate immunoresponse, resulting in the failure of some clinical trials. Therefore, understanding the sophisticated mechanisms of the immunoregulatory function of natural polysaccharides with refined doses for clinical use will help the standardization of traditional medicine.