Lysosome-Mediated Cytotoxic Autophagy Contributes to Tea Polysaccharide-Induced Colon Cancer Cell Death via mTOR-TFEB Signaling

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.