dc.creator | Paunović, Verica | |
dc.creator | Kosić, Milica | |
dc.creator | Ristić, Biljana | |
dc.creator | Bošnjak, Mihajlo | |
dc.creator | Stevanović, Danijela | |
dc.creator | Misirkić Marjanović, Maja | |
dc.creator | Mandić, Miloš | |
dc.creator | Mirčić, Aleksandar | |
dc.creator | Trajković, Vladimir | |
dc.creator | Harhaji-Trajković, Ljubica | |
dc.date.accessioned | 2022-01-19T13:11:21Z | |
dc.date.available | 2900-01-01 | |
dc.date.issued | 2021 | |
dc.identifier.uri | https://www.sfrre2021belgrade.rs/ | |
dc.identifier.uri | http://radar.ibiss.bg.ac.rs/handle/123456789/4728 | |
dc.description.abstract | We investigated the effect of 3-methyladenine (3MA), a class III phosphatidylinositol 3-
kinase (PI3K)-blocking autophagy inhibitor, on the melanoma cell death induced by simultaneous
inhibition of glycolysis by 2-deoxyglucose (2DG) and mitochondrial respiration by rotenone. We
have elsewhere shown that 2DG/rotenone caused oxidative stress, ATP depletion, swelling
of mitochondria, ultimately leading to necrosis. Energy stress is known to induce autophagy,
a tightly regulated self-degradation process, which by recycling damaged organelles and
macromolecules provides building blocks and energy. However, 2DG/rotenone did not induce
proautophagic beclin-1 expression and autophagic flux in melanoma cells despite activation
of AMP-activated protein kinase (AMPK) and subsequent inhibition of mammalian target of
rapamycin complex 1 (mTORC1). 3MA, but not autophagy inhibition with other PI3K and lysosomal
inhibitors, attenuated 2DG/rotenone-induced mitochondrial damage, oxidative stress, ATP
depletion, and cell death. 3MA increased both AMPK and mTORC1 activation in energy stressed
cells, but neither AMPK nor mTORC1 inhibition reduced its cytoprotective effect. 3MA reduced
superoxide generation and c-Jun N-terminal kinase (JNK) activation, and both antioxidant and
JNK blockade mimicked its protective activity. Therefore, 3MA prevents energy stress-triggered
melanoma cell death through autophagy-independent decrease of oxidative stress and JNK
activation. Our results warrant caution in use of 3MA as an autophagy inhibitor. | sr |
dc.language.iso | en | sr |
dc.publisher | Elsevier Inc. | sr |
dc.rights | restrictedAccess | sr |
dc.source | Free Radical Research Europe (SFRR-E) Annual Meeting Abstracts “Redox biology in the 21st century: a new scientific discipline” 15-18 June 2021, Belgrade, Serbia | sr |
dc.title | 3-methyladenine protects melanoma cells against energy stress-induced necrosis by autophagy-independent decrease in oxidative stress and partial involvement of JNK | sr |
dc.type | conferenceObject | sr |
dc.rights.license | ARR | sr |
dc.rights.holder | © 2021 Published by Elsevier Inc. | sr |
dc.description.other | Free Radical Research Europe (SFRR-E): Annual Meeting Abstracts: “Redox biology in the 21st century: a new scientific discipline”; 2021 Jun 15-18; Belgrade, Serbia. Elsevier; 2021. p. S132. (Free Radical Biology and Medicine; Vol. 177; Suppl. 1). | sr |
dc.identifier.doi | 10.1016/j.freeradbiomed.2021.08.223 | |
dc.identifier.wos | 000752898800120 | |
dc.citation.spage | 221 | |
dc.type.version | publishedVersion | sr |
dc.citation.rank | M34 | |