Cnidium officinale polysaccharide enhanced RAW 264.7 cells activation and NK-92 cells cytotoxicity against colon cancer via NF-κB and MAPKs signaling pathways

Kwan Mo Yang; Yunfei Ge; Subramanian Palanisamy; Yutong Zhang; Fang Kou; Khamphone Yelithao; Duyun Jeong; SangGuan You; Seok-Byung Lim

doi:10.1016/j.ijbiomac.2023.127605

Cnidium officinale polysaccharide enhanced RAW 264.7 cells activation and NK-92 cells cytotoxicity against colon cancer via NF-κB and MAPKs signaling pathways

Int J Biol Macromol. 2023 Dec 31;253(Pt 8):127605. doi: 10.1016/j.ijbiomac.2023.127605. Epub 2023 Oct 21.

Authors

Kwan Mo Yang¹, Yunfei Ge², Subramanian Palanisamy³, Yutong Zhang², Fang Kou², Khamphone Yelithao², Duyun Jeong⁴, SangGuan You⁵, Seok-Byung Lim⁶

Affiliations

¹ Department of Surgery, Gangneung Asan Hospital, University of Ulsan College of Medicine, Gangneung, Republic of Korea.
² Department of Marine Food Science and Technology, Gangneung-Wonju National University, 120, Gangneung, Gangwon 210-702, Republic of Korea.
³ Department of Marine Food Science and Technology, Gangneung-Wonju National University, 120, Gangneung, Gangwon 210-702, Republic of Korea; East Coast Life Sciences Institute, Gangneung-Wonju National University, 120, Gangneung, Gangwon 210-702, Republic of Korea.
⁴ Department of Food and Food Service Industry, Kyungpook National University, Sangju 37224, Republic of Korea.
⁵ Department of Marine Food Science and Technology, Gangneung-Wonju National University, 120, Gangneung, Gangwon 210-702, Republic of Korea; East Coast Life Sciences Institute, Gangneung-Wonju National University, 120, Gangneung, Gangwon 210-702, Republic of Korea. Electronic address: umyousg@gwnu.ac.kr.
⁶ Colon and Rectal Surgery, Asan Medical Center and University of Ulsan College of Medicine, Seoul 05505, Republic of Korea. Electronic address: sblim@amc.seoul.kr.

PMID: 37871715
DOI: 10.1016/j.ijbiomac.2023.127605

Abstract

In this study, Cnidium officinale-derived polysaccharides were isolated and investigated for their immune enhancing and anticancer activities. The isolated crude and its fractions, such as F1 and F2, contain carbohydrates (51.3-63.1%), sulfates (5.4-5.8%), proteins (1.5-7.1%), and uronic acids (2.1-26.9%). The molecular weight (M_w) of the polysaccharides ranged from 59.9 to 429.0 × 10³ g/mol. The immunostimulatory activity of the polysaccharides was tested on RAW 264.7 cells, and the results showed that the F2 treatment notably enhanced pro-inflammatory activity in RAW 264.7 cells by increasing NO production and the expression of various cytokines. Furthermore, the influence of polysaccharide treatment on natural killer cells (NK-92) anticancer activities was investigated using a colon cancer cell line (HCT-116). Crude polysaccharide and its fractions showed no direct cytotoxicity to NK-92 and HCT-116 cells. However, the treatment of F2 showed an enhancement of NK-92 cells cytotoxicity against HCT-116 cells by upregulating the mRNA expression of IFN-γ, TNF-α, NKGp44, and granzyme-B. The western blot results showed that the induced RAW 264.7 cells activation and NK-92 cells cytotoxicity occur via NF-κB and MAPK signaling pathways. Overall, C. officinale-derived polysaccharides show potential as immunotherapeutic agents capable of enhancing pro-inflammatory macrophage signaling and activating NK-92 cells; thus, they could be useful for biomedical applications.

Keywords: Anticancer activity; Cnidium officinale; Immunostimulatory activity; Polysaccharides.

MeSH terms

Animals
Cnidium / metabolism
Colonic Neoplasms* / drug therapy
Humans
Mice
NF-kappa B* / metabolism
Polysaccharides / pharmacology
RAW 264.7 Cells
Signal Transduction

Substances

NF-kappa B
Polysaccharides