Agrocybe cylindracea fucoglucogalactan induced lysosome-mediated apoptosis of colorectal cancer cell through H3K27ac-regulated cathepsin D

Ziwei Wang; Kunying Chen; Ke Zhang; Kaihong He; Duoduo Zhang; Xiaohan Guo; Tongwen Huang; Jielun Hu; Xingtao Zhou; Shaoping Nie

doi:10.1016/j.carbpol.2023.121208

Agrocybe cylindracea fucoglucogalactan induced lysosome-mediated apoptosis of colorectal cancer cell through H3K27ac-regulated cathepsin D

Carbohydr Polym. 2023 Nov 1:319:121208. doi: 10.1016/j.carbpol.2023.121208. Epub 2023 Jul 17.

Authors

Affiliations

¹ State Key Laboratory of Food Science and Technology, China-Canada Joint Laboratory of Food Science and Technology (Nanchang), Nanchang University, Nanchang 330047, China.
² State Key Laboratory of Food Science and Technology, China-Canada Joint Laboratory of Food Science and Technology (Nanchang), Nanchang University, Nanchang 330047, China. Electronic address: zhouxingtao@ncu.edu.cn.
³ State Key Laboratory of Food Science and Technology, China-Canada Joint Laboratory of Food Science and Technology (Nanchang), Nanchang University, Nanchang 330047, China. Electronic address: spnie@ncu.edu.cn.

PMID: 37567726
DOI: 10.1016/j.carbpol.2023.121208

Abstract

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.

Keywords: AO: (PubChem CID: 62344); Agrocybe cylindracea fucoglucogalactan; Apoptosis; CTSD; Colorectal cancer; Crystal Violet: (PubChem CID: 11057); DAPI: (PubChem CID: 2954); EB: (PubChem CID: 14710); H3K27ac; Hoechst 33342: (PubChem CID: 1464); Lyso-Tracker Red: (PubChem CID: 15410449); Lysosome; Mito-Tracker Red: (PubChem CID: 22613925); Pep A: (PubChem CID: 5478883); Torin 1: (PubChem CID: 49836027).