The Regulatory Network of Sturgeon Chondroitin Sulfate on Colorectal Cancer Inhibition by Transcriptomic and Proteomic Analysis

Abstract

Chondroitin sulfate (CS) is a food-derived bioactive substance with multiple biological functions, which exists in animal cartilage and/or bone. Sturgeon, a type of cartilaginous fish, is rich in CS. Our recent study demonstrated the effect of sturgeon chondroitin sulfate (SCS) on reducing colorectal cancer cell proliferation and tumor formation. However, the molecular mechanisms of its anticancer activity remain unknown. In this study, the cell proliferation assay and flow cytometric analysis were used to examine the cell viability and apoptosis of colon cancer cell HT-29 cells and normal colonic epithelial cell NCM460 cells. Transcriptomic and proteomic studies were used to identify the main targets of SCS. SCS showed little effect on the genes/proteins expression profile of NCM460 cells but more sensitive to HT-29, in which 188 genes and 10 proteins were differentially expressed after SCS treatment. Enrichment analysis of those genes/proteins showed that the majority of them are involved in DNA replication, cell cycle progression and apoptosis. Quantitative RT-PCR and Western blot were used to determine essential genes/proteins and networks targeted by SCS to exert inhibiting the development of colorectal cancer function. This study provided great insights into developing food-derived novel therapeutics for colorectal cancer treatment.

Sulfation of chondroitin and bile acids converges to antagonize Wnt/β-catenin signaling and inhibit APC deficiency-induced gut tumorigenesis

“…Oral supplementation of CS is well-tolerated by humans with favorable pharmacokinetics. Although CS has shown some beneficial effects to suppress colon cancer cell growth in vitro 48 , 49 , 50 , the molecular mechanism was not defined. Here, we found CS treatment in vitro or in vivo attenuated Papss2 deficiency-induced and APC deficiency-responsive gut tumorigenesis through the inhibition of Wnt/ β -catenin signaling pathway.…”

A novel necroptosis-related lncRNA signature for predicting prognosis and immune response of colon cancer

“…In terms of gene functions and pathways involved in necroptosis-related lncRNAs, previous studies have found that genetic variation in the citric acid cycle and fatty acid metabolism are associated with the onset and progression of CC ( Choi et al, 2019 ; Cho et al, 2020 ). Chondroitin sulfate has certain effects on the proliferation and apoptosis of CC ( Wu et al, 2021 ). The GSEA of this study found that the differentially expressed necroptosis-related lncRNAs in the high-risk group and the low-risk group were involved in the process of gene recombination, tumor cell proliferation, antigen processing and presentation, and nutrient metabolism in CC, thereby affecting the occurrence and progression of CC.…”