Semisynthetic and amylase-treated Taraxacum officinale galactans: Combat colorectal cancer with cytokine modifier response

Abstract

Polysaccharides are naturally abundant, biodegradable, and cost-effective sustainable biomaterials. However, their limited pharmacodynamic properties often hinder clinical efficacy. Hence, structural modifications of polysaccharides can enhance their therapeutic efficacy in response to application demands. In this study, a galactan polysaccharide (TOP₅₀) was purified from Taraxacum officinale, and three derivatives were prepared by sulfation (STOP₅₀), acetylation (ACTOP₅₀), and enzymatic hydrolysis using amylase (TOP_50am). The physicochemical properties were investigated using gas chromatography, size-exclusion chromatography, linkage analysis, infrared spectroscopy, scanning electron microscopy, and ¹H NMR spectroscopy, alongside the determination of the degree of substitution (DSS). The cytotoxic activities of the native and modified polysaccharides were evaluated against colorectal cancer cell lines (HT-29, HCT-116, and RKO), and their immunomodulatory effects were assessed by measuring cytokine levels (IL-6, IL-8, IL-10, and IL-12). Native TOP₅₀ (50 kDa) was identified as a pectic galactan with a chain of 4-linked glucoses (4-Glc), 3,6-linked galactose (3,6-Gal), terminal galactopyranosyl (t-Gal), and glucopyranosyl (t-Glc) residues. Among the derivatives, STOP₅₀ exhibited the most pronounced cytotoxic effect on RKO cells. Both STOP₅₀ and TOP_50am markedly suppressed the expression of pro-inflammatory cytokines IL-8 and IL-10 while significantly enhancing IL-12 production. Remarkably, TOP_50am induced a 15-fold upregulation of IL-12, indicating its potent immunostimulatory effects. These findings highlight the potential of structurally modified T. officinale galactans as multifunctional anticancer agents, supporting their potential in colorectal cancer therapy. The elucidated structure–activity relationships serve as a pivotal basis for developing polysaccharide-based therapeutics aimed at modulating tumor growth and regulating immune responses.