溶酶体
细胞凋亡
TFEB
组织蛋白酶
组织蛋白酶D
细胞生物学
癌细胞
组织蛋白酶B
程序性细胞死亡
癌症研究
细胞色素c
生物
线粒体
化学
分子生物学
癌症
生物化学
自噬
酶
遗传学
作者
Ziwei Wang,Kunying Chen,Ke Zhang,Kaihong He,Duoduo Zhang,Xiaohan Guo,Tongwen Huang,Jielun Hu,Xingtao Zhou,Shaoping Nie
标识
DOI:10.1016/j.carbpol.2023.121208
摘要
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.
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