Cisplatin-induced hydroxyl radicals mediate pro-survival autophagy in human lung cancer H460 cells

Biological research: BR

article

Sumkhemthong, Somruethai¹  Prompetchara, Eakachai²  Chanvorachote, Pithi⁴  Chaotham, Chatchai¹ 

[1] Department of Biochemistry and Microbiology, Faculty of Pharmaceutical Sciences, Chulalongkorn University;Department of Laboratory Medicine, Faculty of Medicine, Chulalongkorn University;Center of Excellence in Vaccine Research and Development (Chula Vaccine Research Center- Chula VRC), Faculty of Medicine, Chulalongkorn University;Department of Pharmacology and Physiology, Faculty of Pharmaceutical Sciences, Chulalongkorn University;Cell-based Drug and Health Products Development Research Unit, Faculty of Pharmaceutical Sciences, Chulalongkorn University

关键词: Cisplatin;    Autophagy;    Drug resistance;    Hydroxyl radicals;    Lung cancer;   

DOI  :  10.1186/s40659-021-00346-2

来源: BioMed Central

【 摘 要 】

Accumulated evidence demonstrates cisplatin, a recommended chemotherapy, modulating pro-survival autophagic response that contributes to treatment failure in lung cancer patients. However, distinct mechanisms involved in cisplatin-induced autophagy in human lung cancer cells are still unclear. Herein, role of autophagy in cisplatin resistance was indicated by a decreased cell viability and increased apoptosis in lung cancer H460 cells pre-incubated with wortmannin, an autophagy inhibitor, prior to treatment with 50 µM cisplatin for 24 h. The elevated level of hydroxyl radicals detected via flow-cytometry corresponded to autophagic response, as evidenced by the formation of autophagosomes and autolysosomes in cisplatin-treated cells. Interestingly, apoptosis resistance, autophagosome formation, and the alteration of the autophagic markers, LC3-II/LC3-I and p62, as well as autophagy-regulating proteins Atg7 and Atg3, induced by cisplatin was abrogated by pretreatment of H460 cells with deferoxamine, a specific hydroxyl radical scavenger. The modulations in autophagic response were also indicated in the cells treated with hydroxyl radicals generated via Fenton reaction, and likewise inhibited by pretreatment with deferoxamine. In summary, the possible role of hydroxyl radicals as a key mediator in the autophagic response to cisplatin treatment, which was firstly revealed in this study would benefit for the further development of novel therapies for lung cancer.

【 授权许可】

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