Chitosan oligosaccharide enhances the anti-cancer effects of 5-fluorouracil on SNU-C5 colorectal cancer cells by activating ERK
JI-SU HAN1, HYE-JIN BOO1, JIN WON HYUN1, HEESANG SONG2, IN-YOUB CHANG3, SANG-PIL YOON1,4,*
1 Jeju Research Center for Natural Medicine, Jeju National University, Jeju, 63243, Republic of Korea
2 Department of Biochemistry and Molecular Biology, Chosun University School of Medicine, Gwangju, 61452, Republic of Korea
3 Department of Anatomy, Chosun University School of Medicine, Gwangju, 61452, Republic of Korea
4 Department of Anatomy, College of Medicine, Jeju National University, Jeju, 63243, Republic of Korea
* Corresponding Author: SANG-PIL YOON. Email: 
Oncology Research https://doi.org/10.32604/or.2024.052003
Received 21 March 2024; Accepted 07 June 2024; Published online 15 July 2024
Abstract
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.
Graphical Abstract
Keywords
Chitosan oligosaccharide (COS); Colorectal cancer (CRC); 5-Fluorouracil (5-FU); ERK (Extracellular signal-regulated protein kinase)
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