1. Academic Validation
  2. Hyperoside suppresses hypoxia-induced A549 survival and proliferation through ferrous accumulation via AMPK/HO-1 axis

Hyperoside suppresses hypoxia-induced A549 survival and proliferation through ferrous accumulation via AMPK/HO-1 axis

  • Phytomedicine. 2020 Feb;67:153138. doi: 10.1016/j.phymed.2019.153138.
Dan Chen 1 Ya-Xian Wu 2 Yu-Bao Qiu 2 Bin-Bin Wan 2 Gang Liu 2 Jun-Liang Chen 2 Mu-Dan Lu 3 Qing-Feng Pang 4
Affiliations

Affiliations

  • 1 School of Food Science and Technology, Jiangnan University, Wuxi 214122, Jiangsu Province, People's Republic of China; Department of physiopathology, Wuxi School of Medicine, Jiangnan University, Wuxi 214002, Jiangsu Province, People's Republic of China.
  • 2 Department of physiopathology, Wuxi School of Medicine, Jiangnan University, Wuxi 214002, Jiangsu Province, People's Republic of China.
  • 3 Central Laboratory, The Affiliated Wuxi Matemity and Child Health Care Hospital of Nanjing Medical University, Wuxi 214122, Jiangsu Province, People's Republic of China. Electronic address: lumudan0527@163.com.
  • 4 Department of physiopathology, Wuxi School of Medicine, Jiangnan University, Wuxi 214002, Jiangsu Province, People's Republic of China. Electronic address: qfpang@jiangnan.edu.cn.
Abstract

Background: Hypoxia is commonly existed in tumors and lead to Cancer cell chemo/radio-resistance. It is well-recognized that tumor hypoxia is a major challenge for the treatment of various solid tumors. Hyperoside (quercetin-3-O-galactoside, Hy) possesses antioxidant effects and has been reported to protect against hypoxia/reoxygenation induced injury in cardiomyocytes. Therefore, Hy may be attractive compound applicable to hypoxia-related diseases.

Purpose: This study was designed to determine the role of Hy in hypoxia-induced proliferation of non-small cell lung Cancer cells and the underlying mechanism.

Study design and methods: A549, a human non-small cell lung Cancer (NSCLC) cell line, was used in the present study. 1% O2 was used to mimic the in vivo hypoxic condition of NSCLC. The potential mechanisms of Hy on hypoxia-induced A549 survival and proliferation, as well as the involvement of AMPK/HO-1 pathway were studied via CCK-8 assay, EdU staining, flow cytometry, qRT-PCR and western blot.

Results: We showed that pretreatment with Hy suppressed hypoxia-induced A549 survival and proliferation in dose-dependent manner. In terms of mechanism, hypoxia-treated A549 showed the lower AMPK phosphorylation and the reduced HO-1 expression, which were reversed by Hy pretreatment. Both AMPK Inhibitor (Compound C) and HO-1 activity inhibitor (Zinc protoporphyrin IX) abolished Hy-evoked A549 cell death under hypoxia stimuli. Of note, Ferrous iron contributed to Hy-induced A549 cell death under hypoxia, while Hy had no effect on lipid peroxidation under hypoxia.

Conclusion: Taken together, our results highlighted the beneficial role of Hy against hypoxia-induced A549 survival and proliferation through ferrous accumulation via AMPK/HO-1 axis.

Keywords

A549; Heme oxygenase-1; Hy; Hypoxia; Survival.

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