Chloroquine Inhibits Deferoxamine-induced Ferritinophagy and Potentiates The Cytotoxicity of Chemotherapy Drugs in Lung Cancer Cells
Chloroquine Inhibits Deferoxamine-induced Ferritinophagy and Potentiates The Cytotoxicity of Chemotherapy Drugs in Lung Cancer Cells
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DOI：
10.16476/j.pibb.2021.0090
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发表时间：
2022
期刊：
影响因子：
--
通讯作者：
Wei Taotao
中科院分区：
文献类型：
--
作者：
Wang Yongwei;Xiao Min;Zhang Yu;Huo Yanwu;Wei Taotao
Objective Lung cancer is one of the most commonly diagnosed cancers and the leading cause of cancer deaths worldwide.Despite significant advancements in combined therapy,the numbers of lung cancer cases and deaths continue to rise. Thus,novel therapeutic strategies are necessary to improve cure rates.Methods The effect of concomitant use of deferoxamine and chloroquine with frontline chemotherapy drugs was evaluated in lung cancer cells.The autophagy-dependent degradation of ferritin(i.e.ferritinophagy)was determined by western blot and immunofluorescence.The cell proliferation was quantified by cell member and cell cycle.The mitochondrial oxidative phosphorylation was determined by measuring the cellular oxygen consumption. Results The iron chelator deferoxamine induced ferritinophagy in cancer cells,and this process was blocked by chloroquine,an anti-malaria drug.Exposure of lung cancer cells to deferoxamine and chloroquine together inhibited mitochondrial oxidative phosphorylation,caused the accumulation of G1 phase cells and blocked cell proliferation.More importantly,the use of deferoxamine and chloroquine concomitantly with cisplatin or etoposide resulted in a significant increase in cytotoxicity in lung cancer cells when compared with the same concentration of cisplatin or etoposide alone.Conclusion These data indicate the efficacy of targeting ferritinophagy for the sensitization of iron-addicted cancer cells to chemotherapy,and introduce a potential targeted therapeutic approach for the treatment of cancer.
