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Taxonomic group: fungi / Basidiomycota (Phylum: Basidiomycota)
Organ / tissue: fruiting bodies

NCBI PubMed ID: 37567726
Publication DOI: 10.1016/j.carbpol.2023.121208
Journal NLM ID: 8307156
Publisher: Elsevier
Correspondence: X. Zhou <zhouxingtao

ncu.edu.cn>; S. Nie <spnie

ncu.edu.cn>
Institutions: State Key Laboratory of Food Science and Technology, China-Canada Joint Laboratory of Food Science and Technology (Nanchang), Nanchang University, Nanchang 330047, China

Inducing lysosomal dysfunction is emerging as a promising means for cancer therapy. Agrocybe cylindracea fucoglucogalactan (ACP) is a bioactive ingredient with anti-tumor activity, while its mechanism remains obscure. Herein, we found that ACP visibly inhibited the proliferation of colorectal cancer cells, and the IC50 value on HCT-116 cells (HT29 cells) was 490 μg/mL (786.4 μg/mL) at 24 h. RNA-seq showed that ACP regulated mitochondria, lysosome and apoptosis-related pathways. Further experiments proved that ACP indeed promoted apoptosis and lysosomal dysfunction of HCT-116 cells. Moreover, ChIP-seq revealed that ACP increased histone-H3-lysine-27 acetylation (H3K27ac) on CTSD (cathepsin D) promoter in HCT-116 cells, thus facilitating the binding of transcription factor EB (TFEB), and resulted in ascension of CTSD expression. Additionally, ACP triggered mitochondrial-mediated apoptosis by decreasing mitochondrial membrane potential and increasing pro-apoptotic protein levels. Notably, Pepstatin A (CTSD inhibitor) availably alleviated ACP-induced apoptosis. Taken together, our results indicated that ACP induced lysosome-mitochondria mediated apoptosis via H3K27ac-regulated CTSD in HCT-116 cells. This study indicates that ACP has anti-cancer potential in the treatment of colorectal cancer.

apoptosis, colorectal cancer, Agrocybe cylindracea fucoglucogalactan, CTSD, H3K27ac, lysosome

Structure type: structural motif or average structure ; 156000
Location inside paper: p. 37567726-2
Trivial name: polysaccharide SACP-80, fucoglucogalactan (ACP), polysaccharide SACP-80
Contained glycoepitopes: IEDB_115015,IEDB_134624,IEDB_135614,IEDB_136045,IEDB_136906,IEDB_137472,IEDB_140529,IEDB_141794,IEDB_141806,IEDB_142488,IEDB_142489,IEDB_144562,IEDB_146664,IEDB_149135,IEDB_151528,IEDB_152214,IEDB_153553,IEDB_167069,IEDB_174333,IEDB_190606,IEDB_241101,IEDB_983931,SB_154,SB_163,SB_192,SB_7,SB_86

Methods: Western blotting, statistical analysis, RNA sequencing, cell proliferation assay, immunofluorescence, staining, cell culture, cathepsin D activity assay
Biological activity: ACP increased H3K27ac on the promoter of gene CTSD in HCT-116 cells, thereby promoting the binding of TFEB, subsequently activating CTSD gene transcription and promoting lysosome accumulation.
Comments, role: structure from ref. Wang Y.X., et al., Food Hydrocolloids, 2021, 114, 106568, DOI: 10.1016/j.foodhyd.2020.106568.

NCBI Taxonomy refs (TaxIDs): 1593264
Show glycosyltransferases

There are 64 chemically distinct structures. Please, select:

*OC[C@H]1O[C@H](OC[C@H]2O[C@H](OC[C@H]3O[C@@H](OC[C@H]4O[C@@H](OC[C@H]5O[C@@H](*)[C@H](O)[C@@H](O)[C@@H]5O)[C@H](O)[C@@H](O)[C@@H]4O)[C@H](O)[C@@H](O)[C@@H]3O)[C@H](O[C@H]3O[C@H](C)[C@H](O)[C@H](O)[C@H]3O)[C@@H](O)[C@H]2O)[C@H](O)[C@@H](O)[C@H]1O

SVG MW SMILES 3D mol Ionize