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

Ke Zhang; Duoduo Zhang; Junqiao Wang; Yuting Wang; Jiarui Hu; Yujia Zhou; Xingtao Zhou; Shaoping Nie; Mingyong Xie

doi:10.1016/j.carbpol.2022.119841

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. Epub 2022 Jul 8.

Authors

Ke Zhang¹, Duoduo Zhang¹, Junqiao Wang¹, Yuting Wang¹, Jiarui Hu¹, Yujia Zhou¹, Xingtao Zhou², Shaoping Nie¹, Mingyong Xie³

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: zhouxingtao@ncu.edu.cn.
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: myxie@ncu.edu.cn.

PMID: 35989033
DOI: 10.1016/j.carbpol.2022.119841

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.

MeSH terms

Aloe*
Antineoplastic Agents* / pharmacology
Antineoplastic Agents* / therapeutic use
Cell Death
Colonic Neoplasms* / drug therapy
Colonic Neoplasms* / genetics
Colonic Neoplasms* / metabolism
Humans
Mannans
Mitochondria / drug effects
Mitochondria / genetics
Mitochondria / metabolism
Mitophagy / drug effects
Mitophagy / genetics
Mitophagy / physiology
Protein Kinases* / genetics
Protein Kinases* / metabolism
Reactive Oxygen Species / metabolism
Ubiquitin-Protein Ligases* / genetics
Ubiquitin-Protein Ligases* / metabolism

Substances

Antineoplastic Agents
Mannans
Reactive Oxygen Species
(1-6)-alpha-glucomannan
Ubiquitin-Protein Ligases
parkin protein
Protein Kinases
PTEN-induced putative kinase