Lysosome-Mediated Cytotoxic Autophagy Contributes to Tea Polysaccharide-Induced Colon Cancer Cell Death via mTOR-TFEB Signaling.
Yujia ZhouXingtao ZhouXiaojun HuangTao HongKe ZhangWucheng QiMi GuoShao-Ping NiePublished in: Journal of agricultural and food chemistry (2020)
Targeting autophagy and lysosome may serve as a promising strategy for cancer therapy. Tea polysaccharide (TP) has shown promising antitumor effects. However, its mechanism remains elusive. Here, TP was found to have a significant inhibitory effect on the proliferation of colon cancer line HCT116 cells. RNA-seq analysis showed that TP upregulated autophagy and lysosome signal pathways, which was further confirmed through experiments. Immunofluorescence experiments indicated that TP activated transcription factor EB (TFEB), a key nuclear transcription factor modulating autophagy and lysosome biogenesis. In addition, TP inhibited the activity of mTOR, while it increased the expression of Lamp1. Furthermore, TP ameliorated the lysosomal damage and autophagy flux barrier caused by Baf A1 (lysosome inhibitor). Hence, our data suggested that TP repressed the proliferation of HCT116 cells by targeting lysosome to induce cytotoxic autophagy, which might be achieved through mTOR-TFEB signaling. In summary, TP may be used as a potential drug to overcome colon cancer.
Keyphrases
- cell death
- cell cycle arrest
- signaling pathway
- endoplasmic reticulum stress
- fluorescent probe
- oxidative stress
- transcription factor
- induced apoptosis
- living cells
- rna seq
- cancer therapy
- cell proliferation
- single cell
- poor prognosis
- machine learning
- risk assessment
- artificial intelligence
- long non coding rna
- data analysis
- climate change