Dexmedetomidine promotes autophagy and apoptosis of colon cancer cells by activating endoplasmic reticulum (ER) stress-mediated PERK/eIF2α/ATF4 signaling pathway

• Published in: Molecular & cellular toxicology Vol. 20; no. 3; pp. 495 - 507
• Main Authors: Hou, Xiaochao, Jiang, Yujie, Xu, Guiping
• Format: Journal Article
• Language: English
• Published: Singapore Springer Nature Singapore 01.07.2024; 대한독성 유전단백체 학회
• Subjects: Biomedical and Life Sciences; Cell Biology; Life Sciences; Original Article; Pharmacology/Toxicology; 생물학; Colon cancer; Autophagy; Dexmedetomidine; Apoptosis; Endoplasmic reticulum stress
• ISSN: 1738-642X; 2092-8467
• DOI: 10.1007/s13273-023-00363-0

Background Colon cancer is a malignancy from digestive tract and remains the third most common cancer worldwide. Dexmedetomidine (DEX) can be used for postoperative analgesia in patients with colon cancer and also has biological activities such as anti-oxidative stress, anti-inflammation, and anti-cancer. Objective This study was designed to explore the functions and mechanism of DEX in regulating colon cancer cell proliferation, apoptosis, and autophagy. Results Dex reduced LoVo and HCT116 cell viability in a time- and dose-dependent way. Additionally, DEX suppressed colon cancer cell proliferation while promoting cell apoptosis and autophagy. Moreover, chloroquine (a compound used for inhibition of autophagy) reversed the promoting effect of DEX on colon cancer cell apoptosis. Furthermore, DEX activated the protein kinase RNA-like endoplasmic reticulum kinase (PERK)/eukaryotic initiation factor 2 alpha (eIF2α)/activating transcription factor 4 (ATF4) signaling pathway. PERK silencing inhibited DEX-induced cell apoptosis and autophagy. Conclusion This work revealed the anti-cancer effect of DEX treatment by inhibiting colon cancer cell proliferation while promoting cancer cell apoptosis and autophagy via the PERK/eIF2α/ATF4 pathway.