dc.creator | Kosić, Milica | |
dc.creator | Paunović, Verica | |
dc.creator | Ristić, Biljana | |
dc.creator | Mirčić, Aleksandar | |
dc.creator | Bošnjak, Mihajlo | |
dc.creator | Stevanović, Danijela | |
dc.creator | Kravić-Stevović, Tamara K | |
dc.creator | Trajković, Vladimir | |
dc.creator | Harhaji-Trajković, Ljubica | |
dc.date.accessioned | 2021-10-04T07:35:48Z | |
dc.date.available | 2021-10-04T07:35:48Z | |
dc.date.issued | 2021 | |
dc.identifier.issn | 1347-8613 | |
dc.identifier.uri | https://www.sciencedirect.com/science/article/pii/S1347861321000591 | |
dc.identifier.uri | https://radar.ibiss.bg.ac.rs/handle/123456789/4427 | |
dc.description.abstract | We investigated the effect of 3-methyladenine (3MA), a class III phosphatidylinositol 3-kinase (PI3K)-blocking autophagy inhibitor, on cancer cell death induced by simultaneous inhibition of glycolysis by 2-deoxyglucose (2DG) and mitochondrial respiration by rotenone. 2DG/rotenone reduced ATP levels and increased mitochondrial superoxide production, causing mitochondrial swelling and necrotic death in various cancer cell lines. 2DG/rotenone failed to increase proautophagic beclin-1 and autophagic flux in melanoma cells despite the activation of AMP-activated protein kinase (AMPK) and inhibition of mechanistic 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, while antioxidant treatment mimicked its protective action. The protection was not mediated by autophagy upregulation via class I PI3K/Akt inhibition, as it was preserved in cells with genetically inhibited autophagy. 3MA increased AMPK and mTORC1 activation in energy-stressed cells, but neither AMPK nor mTORC1 inhibition reduced its cytoprotective effect. 3MA reduced JNK activation, and JNK pharmacological/genetic suppression mimicked its mitochondria-preserving and cytoprotective activity. Therefore, 3MA prevents energy stress-triggered cancer cell death through autophagy-independent mechanisms possibly involving JNK suppression and decrease of oxidative stress. Our results warrant caution when using 3MA as an autophagy inhibitor. | sr |
dc.language.iso | en | sr |
dc.publisher | Kyoto : Japanese Pharmacological Society | sr |
dc.relation | UNESCO L'OREAL national scholarship program "For Women in Science", Grant No. 403F | sr |
dc.relation | info:eu-repo/grantAgreement/MESTD/inst-2020/200007/RS// | sr |
dc.relation | info:eu-repo/grantAgreement/MESTD/inst-2020/200110/RS// | sr |
dc.rights | openAccess | sr |
dc.rights.uri | https://creativecommons.org/licenses/by/4.0/ | |
dc.source | Journal of Pharmacological Sciences | sr |
dc.subject | 3-Methyladenine | sr |
dc.subject | Glycolysis | sr |
dc.subject | Mitochondria | sr |
dc.subject | Autophagy | sr |
dc.subject | Necrosis | sr |
dc.title | 3-Methyladenine prevents energy stress-induced necrotic death of melanoma cells through autophagy-independent mechanisms | sr |
dc.type | article | sr |
dc.rights.license | BY-NC-ND | sr |
dcterms.abstract | Трајковић, Владимир; Косић, Милица; Пауновић, Верица; Ристић, Биљана; Мирчић, Aлександар; Стевановић, Данијела; Бошњак, Михајло; Хархаји Трајковић, Љубица; Кравић-Стевовић, Тамара К; | |
dc.rights.holder | © 2021 The Authors. Production and hosting by Elsevier B.V. on behalf of Japanese Pharmacological Society. | sr |
dc.citation.issue | 1 | |
dc.citation.volume | 147 | |
dc.identifier.doi | 10.1016/j.jphs.2021.06.003 | |
dc.identifier.pmid | 34294367 | |
dc.identifier.scopus | 2-s2.0-85109000842 | |
dc.identifier.wos | 000674666800021 | |
dc.citation.apa | Kosic, M., Paunovic, V., Ristic, B., Mircic, A., Bosnjak, M., Stevanovic, D., et al. (2021). 3-Methyladenine prevents energy stress-induced necrotic death of melanoma cells through autophagy-independent mechanisms. Journal of Pharmacological Sciences, 147(1), 156–167. | |
dc.citation.vancouver | Kosic M, Paunovic V, Ristic B, Mircic A, Bosnjak M, Stevanovic D, Kravic-Stevovic T, Trajkovic V, Harhaji-Trajkovic L. 3-Methyladenine prevents energy stress-induced necrotic death of melanoma cells through autophagy-independent mechanisms. J Pharmacol Sci. 2021;147(1):156–67. | |
dc.citation.spage | 156 | |
dc.citation.epage | 167 | |
dc.type.version | publishedVersion | sr |
dc.identifier.fulltext | https://radar.ibiss.bg.ac.rs/bitstream/id/9132/1-s2.0-S1347861321000591-main.pdf | |
dc.citation.rank | M22 | |