1. Academic Validation
  2. Aloe gel glucomannan induced colon cancer cell death via mitochondrial damage-driven PINK1/Parkin mitophagy pathway

Aloe gel glucomannan induced colon cancer cell death via mitochondrial damage-driven PINK1/Parkin mitophagy pathway

  • Carbohydr Polym. 2022 Nov 1:295:119841. doi: 10.1016/j.carbpol.2022.119841.
Ke Zhang 1 Duoduo Zhang 1 Junqiao Wang 1 Yuting Wang 1 Jiarui Hu 1 Yujia Zhou 1 Xingtao Zhou 2 Shaoping Nie 1 Mingyong Xie 3
Affiliations

Affiliations

  • 1 State Key Laboratory of Food Science and Technology, China-Canada Joint Laboratory of Food Science and Technology (Nanchang), Key Laboratory of Bioactive Polysaccharides of Jiangxi Province, Nanchang University, China.
  • 2 State Key Laboratory of Food Science and Technology, China-Canada Joint Laboratory of Food Science and Technology (Nanchang), Key Laboratory of Bioactive Polysaccharides of Jiangxi Province, Nanchang University, China. Electronic address: [email protected].
  • 3 State Key Laboratory of Food Science and Technology, China-Canada Joint Laboratory of Food Science and Technology (Nanchang), Key Laboratory of Bioactive Polysaccharides of Jiangxi Province, Nanchang University, China. Electronic address: [email protected].
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.

Keywords

Aloe gel glucomannan; Ammonium sulfate (PubChem CID: 6097028); Crystal Violet (PubChem CID: 11057); DAPI (PubChem CID: 2954); Ethanol (PubChem CID: 702); FCCP (PubChem CID: 3330); Hoechst 33342 (PubChem CID: 1464); Mdivi-1 (PubChem CID: 3825829); MitoTracker Red (PubChem CID: 22613925); Mitophagy; N-Acetyl-L-cysteine (PubChem CID: 12035); Phenol (PubChem CID: 996); ROS; Rapamycin (PubChem CID: 5284616); Sulfuric Acid (PubChem CID: 1118); TFEB; Triton X-100 (PubChem CID: 5590); colon cancer.

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