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

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.

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.

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.

These results suggest that COS might enhance the anti-cancer effects of 5-FU in SNU-C5 colorectal cancer cells by activating ERK.