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.
Highlights
Colorectal cancer (CRC) is a common digestive tract cancer with increasing incidence rate and mortality rate worldwide in recent years [1]
sturgeon chondroitin sulfate (SCS) showed little cytotoxicity on normal colon cell line NCM460 (8.77 ± 0.02%). These results indicate that the inhibitory activity of SCS is specific to colon cancer cells, and has no toxicity to normal colon cells NCM460
The IC50 results show that the IC50 values of SCS on five kinds of colorectal cancer cells were close, indicating that SCS had a general inhibitory effect on the proliferation of colorectal cancer, and had little toxicity to normal intestinal cell NCM460
Summary
Colorectal cancer (CRC) is a common digestive tract cancer with increasing incidence rate and mortality rate worldwide in recent years [1]. Chondroitin sulfate (CS) is the main active component in animal cartilage. CS has a variety of biological activities such as regulating cell viability and maintaining the integrity of tissue structure [8,9,10,11] They have been widely used for medical and health purposes, such as the treatment of osteoarthritis, cardiovascular diseases and tissue regeneration. The in vivo and in vitro data from our previous study show that CS can inhibit the proliferation of HCT-116 cells by inducing apoptosis, which suggests that CS has antitumor activity against colorectal cancer [13]. We used HT-29 cells as the CRC cancer model cells to investigate the antitumor mechanisms of a hybrid sturgeon (Acipenser schrenckii × Huso dauricus)-derived chondroitin sulfates (SCS). The key genes/proteins in networks targeted by SCS to inhibit the occurrence of CRC were detected by quantitative RT-PCR and Western blot as well as to study the underlying molecular mechanisms
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