Chitosan oligosaccharide enhances the anti-cancer effects of 5-fluorouracil on SNU-C5 colorectal cancer cells by activating ERK.

BACKGROUND: Chitosan oligosaccharide (COS) is the major degradation product of chitosan by enzymatic processes. COS, with complete water solubility, exerts significant biological effects, including anti-cancer activity. We investigated the anti-tumor effects of COS on colorectal cancer as effective therapeutic methods with low side effects are lacking. METHODS: COS was obtained from low molecular weight chitosan by an enzymatic method and the anti-cancer effects were measured by cell viability assay, flow cytometry analysis, Western blotting, and xenograft. RESULTS: COS suppressed the proliferation of SNU-C5 cells compared to other colorectal cancer cells, but higher concentrations were required in the xenograft model. Co-treatment with 5-fluorouracil (5-FU) and COS enhanced the anti-cancer effects of 5-FU in SNU-C5 cells in vitro and in vivo. Flow cytometry revealed that COS induced cell cycle arrest at the G0/G1 phase without 5-FU or at the S and G2/M phases with 5-FU but did not affect cell death pathways. COS increased extracellular signal-regulated protein kinase (ERK) activation with or without 5-FU, whereas 5-FU treatment increased p53 activation. A low-dose of an ERK inhibitor suppressed COS-induced ERK activation and resulted in higher proliferation compared with COS. CONCLUSIONS: These results suggest that COS might enhance the anti-cancer effects of 5-FU in SNU-C5 colorectal cancer cells by activating ERK.