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

Abstract Background: 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 ar...

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Autores principales:	Sumkhemthong,Somruethai, Prompetchara,Eakachai, Chanvorachote,Pithi, Chaotham,Chatchai
Lenguaje:	English
Publicado:	Sociedad de Biología de Chile 2021
Materias:	Cisplatin Autophagy Drug resistance Hydroxyl radicals Lung cancer
Acceso en línea:	http://www.scielo.cl/scielo.php?script=sci_arttext&pid=S0716-97602021000100220
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spelling	oai:scielo:S0716-976020210001002202021-08-16Cisplatin-induced hydroxyl radicals mediate pro-survival autophagy in human lung cancer H460 cellsSumkhemthong,SomruethaiPrompetchara,EakachaiChanvorachote,PithiChaotham,Chatchai Cisplatin Autophagy Drug resistance Hydroxyl radicals Lung cancer Abstract Background: 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. Results: 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. Conclusions: 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.info:eu-repo/semantics/openAccessSociedad de Biología de ChileBiological Research v.54 20212021-01-01text/htmlhttp://www.scielo.cl/scielo.php?script=sci_arttext&pid=S0716-97602021000100220en10.1186/s40659-021-00346-2
institution	Scielo Chile
collection	Scielo Chile
language	English
topic	Cisplatin Autophagy Drug resistance Hydroxyl radicals Lung cancer
spellingShingle	Cisplatin Autophagy Drug resistance Hydroxyl radicals Lung cancer Sumkhemthong,Somruethai Prompetchara,Eakachai Chanvorachote,Pithi Chaotham,Chatchai Cisplatin-induced hydroxyl radicals mediate pro-survival autophagy in human lung cancer H460 cells
description	Abstract Background: 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. Results: 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. Conclusions: 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.
author	Sumkhemthong,Somruethai Prompetchara,Eakachai Chanvorachote,Pithi Chaotham,Chatchai
author_facet	Sumkhemthong,Somruethai Prompetchara,Eakachai Chanvorachote,Pithi Chaotham,Chatchai
author_sort	Sumkhemthong,Somruethai
title	Cisplatin-induced hydroxyl radicals mediate pro-survival autophagy in human lung cancer H460 cells
title_short	Cisplatin-induced hydroxyl radicals mediate pro-survival autophagy in human lung cancer H460 cells
title_full	Cisplatin-induced hydroxyl radicals mediate pro-survival autophagy in human lung cancer H460 cells
title_fullStr	Cisplatin-induced hydroxyl radicals mediate pro-survival autophagy in human lung cancer H460 cells
title_full_unstemmed	Cisplatin-induced hydroxyl radicals mediate pro-survival autophagy in human lung cancer H460 cells
title_sort	cisplatin-induced hydroxyl radicals mediate pro-survival autophagy in human lung cancer h460 cells
publisher	Sociedad de Biología de Chile
publishDate	2021
url	http://www.scielo.cl/scielo.php?script=sci_arttext&pid=S0716-97602021000100220
work_keys_str_mv	AT sumkhemthongsomruethai cisplatininducedhydroxylradicalsmediateprosurvivalautophagyinhumanlungcancerh460cells AT prompetcharaeakachai cisplatininducedhydroxylradicalsmediateprosurvivalautophagyinhumanlungcancerh460cells AT chanvorachotepithi cisplatininducedhydroxylradicalsmediateprosurvivalautophagyinhumanlungcancerh460cells AT chaothamchatchai cisplatininducedhydroxylradicalsmediateprosurvivalautophagyinhumanlungcancerh460cells
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Cisplatin-induced hydroxyl radicals mediate pro-survival autophagy in human lung cancer H460 cells

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