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Mitophagy can selectively remove damaged mitochondria, which is critical in regulating mitochondrial homeostasis in diseases, such as cancer. Herein, we found that Aloe gel glucomannan (AGP) significantly inhibited the proliferation of colon cancer cells. RNA-seq analysis revealed that AGP upregulated autophagy, lysosome and mitochondrial fission signal pathways in colon cancer cell line CT26. Notably, AGP induced the accumulation of impaired and reactive oxygen species (ROS)-generating mitochondria, which triggered excessive mitophagy. Interestingly, the mitophagy activator enhanced AGP-induced mitophagy and cytotoxicity, whereas the mitophagy inhibitor reversed the influence of AGP. Furthermore, activation of PINK1/Parkin mitophagy pathway and transcription factor EB (TFEB) signaling was dependent on ROS overproduction. Taken together, these results indicated that AGP induced cytotoxic mitophagy through ROS-related PINK1/Parkin pathway and TFEB activation in CT26 cells. The research would provide theoretical basis for the development of AGP as a promising anticancer agent. [Display omitted] [ABSTRACT FROM AUTHOR]

[Display omitted] • Dendrobium officinale Polysaccharide (DOP) inhibits colon cancer cells growth. • DOP triggers autophagy, oxidative stress and AMPK signaling in colon cancer cells. • DOP-induced Mitochondrial damage causes autophagic cell death via ROS-AMPK pathway. The homeostasis between mitochondrial function and autophagy is crucial to the physiological activity of cancer cells, and its mechanism is conducive to the development of anti-tumor drugs. Here, we aimed to explore the effect and mechanism of Dendrobium officinale polysaccharide (DOP) on colon cancer cell line CT26. Our data showed that DOP significantly inhibited the proliferation of CT26 cells and elevated autophagy level. Moreover, DOP disrupted mitochondrial function through increasing reactive oxygen species (ROS) and reducing mitochondrial membrane potential (MMP), thereby impairing ATP biosynthesis, which activated AMPK/mTOR autophagy signaling. Intriguingly, the further experiments demonstrated that DOP-induced cytotoxicity, excessive autophagy and mitochondrial dysfunction were reversed after CT26 cells pretreated with antioxidant (N-acetyl- l -cysteine). Herein, these findings implied that DOP-induced mitochondrial dysfunction and cytotoxic autophagy repressed the propagation of CT26 cells via ROS-ATP-AMPK signaling, providing a new opinion for the study of antineoplastic drugs. [ABSTRACT FROM AUTHOR]

• Cordyceps sinensis polysaccharide (CSP) inhibited the growth of colon cancer cells. • CSP induced apoptosis and autophagy flux blockage in colon cancer cells. • Autophagy inhibition increased CSP-induced apoptosis in colon cancer cells. Cordyceps sinensis is thought to have anti-cancer effects, but its mechanisms remain elusive. In this study, we aimed to investigate the anti-cancer effect of Cordyceps sinensis polysaccharide (CSP) on human colon cancer cell line (HCT116) and its mechanism. Results indicated that CSP significantly inhibited the proliferation of HCT116 cells, increased autophagy and apoptosis, while blocked autophagy flux and lysosome formation. Further experiments showed that CSP decreased the expression of PI3K and phosphorylation level of AKT and mTOR, increased the expression of AMPKa and phosphorylation level of ULK1. In addition, repression of CSP-induced autophagy by bafilomycin (autophagy inhibitor) enhanced apoptosis and cell death of HCT116 cells. Hence, our findings suggested that CSP inhibited the proliferation of HCT116 cells by inducing apoptosis and autophagy flux blockage, which might be achieved through PI3K-AKT-mTOR and AMPK-mTOR-ULK1 signaling. CSP may be a potential therapeutic agent for colon cancer. [ABSTRACT FROM AUTHOR]