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Hyperoside suppresses hypoxia-induced A549 survival and proliferation through ferrous accumulation via AMPK/HO-1 axis.
Phytomedicine ( IF 6.7 ) Pub Date : 2019-11-18 , 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 2
Phytomedicine ( IF 6.7 ) Pub Date : 2019-11-18 , 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 2
Affiliation
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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.
中文翻译：
Hyperoside通过AMPK / HO-1轴通过亚铁累积抑制缺氧诱导的A549存活和增殖。
背景技术缺氧通常存在于肿瘤中，并导致癌细胞的化学/放射抗性。众所周知，肿瘤缺氧是治疗各种实体瘤的主要挑战。Hyperoside（槲皮素-3-O-半乳糖苷，Hy）具有抗氧化作用，据报道可防止缺氧/复氧引起的心肌损伤。因此，Hy可能是适用于缺氧相关疾病的有吸引力的化合物。目的本研究旨在确定Hy在缺氧诱导的非小细胞肺癌细胞增殖中的作用及其潜在机制。研究设计与方法A549是一种人类非小细胞肺癌（NSCLC）细胞系，用于本研究。1％O2用于模拟NSCLC的体内低氧状况。通过CCK-8检测，EdU染色，流式细胞仪，qRT-PCR和western blot研究了Hy对缺氧诱导的A549存活和增殖以及AMPK / HO-1途径参与的潜在机制。结果我们显示，Hy预处理以剂量依赖的方式抑制了缺氧诱导的A549存活和增殖。在机理上，低氧处理的A549显示出较低的AMPK磷酸化和降低的HO-1表达，这被Hy预处理逆转。AMPK抑制剂（化合物C）和HO-1活性抑制剂（锌原卟啉IX）均消除了缺氧刺激下Hy-诱发的A549细胞死亡。值得注意的是，亚铁在低氧条件下导致Hy诱导的A549细胞死亡，而Hy在低氧条件下对脂质过氧化没有影响。结论综上所述，
更新日期：2019-11-18
中文翻译：
Hyperoside通过AMPK / HO-1轴通过亚铁累积抑制缺氧诱导的A549存活和增殖。
背景技术缺氧通常存在于肿瘤中，并导致癌细胞的化学/放射抗性。众所周知，肿瘤缺氧是治疗各种实体瘤的主要挑战。Hyperoside（槲皮素-3-O-半乳糖苷，Hy）具有抗氧化作用，据报道可防止缺氧/复氧引起的心肌损伤。因此，Hy可能是适用于缺氧相关疾病的有吸引力的化合物。目的本研究旨在确定Hy在缺氧诱导的非小细胞肺癌细胞增殖中的作用及其潜在机制。研究设计与方法A549是一种人类非小细胞肺癌（NSCLC）细胞系，用于本研究。1％O2用于模拟NSCLC的体内低氧状况。通过CCK-8检测，EdU染色，流式细胞仪，qRT-PCR和western blot研究了Hy对缺氧诱导的A549存活和增殖以及AMPK / HO-1途径参与的潜在机制。结果我们显示，Hy预处理以剂量依赖的方式抑制了缺氧诱导的A549存活和增殖。在机理上，低氧处理的A549显示出较低的AMPK磷酸化和降低的HO-1表达，这被Hy预处理逆转。AMPK抑制剂（化合物C）和HO-1活性抑制剂（锌原卟啉IX）均消除了缺氧刺激下Hy-诱发的A549细胞死亡。值得注意的是，亚铁在低氧条件下导致Hy诱导的A549细胞死亡，而Hy在低氧条件下对脂质过氧化没有影响。结论综上所述，
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