Aloe gel glucomannan induced colon cancer cell death via mitochondrial damage-driven PINK1/Parkin mitophagy pathway. (1st November 2022)

• Record Type: Journal Article
• Authors: Zhang, Ke; Zhang, Duoduo; Wang, Junqiao; Wang, Yuting; Hu, Jiarui; Zhou, Yujia; Zhou, Xingtao; Nie, Shaoping; Xie, Mingyong
• Is Part Of: Carbohydrate polymers. Volume 295(2022)
• Publication Date: 2022-11-01
• Subjects: Aloe gel glucomannan -- colon cancer -- Mitophagy -- ROS -- TFEB; N-Acetyl-L-cysteine (PubChem CID: 12035) -- FCCP (PubChem CID: 3330) -- Rapamycin (PubChem CID: 5284616) -- Mdivi-1 (PubChem CID: 3825829) -- Hoechst 33342 (PubChem CID: 1464) -- Ethanol (PubChem CID: 702) -- Ammonium sulfate (PubChem CID: 6097028) -- Phenol (PubChem CID: 996) -- Sulfuric Acid (PubChem CID: 1118) -- MitoTracker Red (PubChem CID: 22613925) -- Crystal Violet (PubChem CID: 11057) -- Triton X-100 (PubChem CID: 5590) -- DAPI (PubChem CID: 2954); Polysaccharides -- Periodicals; Polysaccharides -- Periodicals; Polysaccharides -- Périodiques; Electronic journals; 547.78
• DOI: 10.1016/j.carbpol.2022.119841
• Languages: English
• ISSNs: 0144-8617

Abstract

Abstract: 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. Graphical abstract: Unlabelled Image