TY  - EJOU
AU  - HAN, JI-SU 
AU  - BOO, HYE-JIN 
AU  - HYUN, JIN WON 
AU  - SONG, HEESANG 
AU  - CHANG, IN-YOUB 
AU  - YOON, SANG-PIL 

TI  - Chitosan oligosaccharide enhances the anti-cancer effects of 5-fluorouracil on SNU-C5 colorectal cancer cells by activating ERK
T2  - Oncology Research

PY  - 2025
VL  - 33
IS  - 4
SN  - 1555-3906

AB  -  <b>Background:</b> 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. <b>Methods:</b> 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. <b>Results:</b> 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 <i>in vitro</i> and <i>in vivo</i>. 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. <b>Conclusions:</b> These results suggest that COS might enhance the anti-cancer effects of 5-FU in SNU-C5 colorectal cancer cells by activating ERK.
KW  - Chitosan oligosaccharide (COS); Colorectal cancer (CRC); 5-Fluorouracil (5-FU); ERK (Extracellular signal-regulated protein kinase)

DO  - 10.32604/or.2024.052003