Lysosome-mediated mitochondrial apoptosis induced by tea polysaccharides promotes colon cancer cell death.

The release of lysosomal hydrolase into the cytoplasm is accompanied by several systems of apoptosis signal transduction, and the imbalance between cell viability and apoptosis induces tumorigenesis. Tea polysaccharides (TPs) are the main bioactive components in green tea with hopeful anti-tumor efficacy, while their mechanism is still unclear. Here, TPs significantly promoted the death of colon cancer cell line CT26. RNA-seq results showed that the signal pathways up-regulated by TPs included lysosome pathways, apoptosis, the release of mitochondrial pigment c and programmed cell death. Among them, the results of AO-EB and annexin V-FITC/PI double staining indicated that TPs significantly up-regulated apoptosis. In addition, TPs significantly disrupted the function of lysosomes, which would cause mitochondrial damage. Intriguingly, TPs treatment increased the expression of Bak1, cleaved caspase-9 and cleaved caspase-3, but decreased the level of Bcl-2 and mitochondrial membrane potential, which indicated that TPs induced mitochondrial-mediated apoptosis. Moreover, TPs ameliorated the reduced lysosomal numbers by Baf A1 (lysosomal inhibitor). Therefore, our data indicated that TPs targeted lysosomes and induced apoptosis by a lysosomal-mitochondrial pathway mediated caspase cascade, thereby inhibiting the proliferation of CT26 cells. In short, the data would help the development of TPs as potential cancer drug therapeutics.

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.