Приказ основних података о документу
Dual targeting of energy metabolism and lysosomes as an anticancer strategy; It is not all about autophagy
dc.contributor | Đorđić Crnogorac, Marija | |
dc.contributor | Nedeljković, Milica | |
dc.creator | Harhaji-Trajković, Ljubica | |
dc.creator | Kosić, Milica | |
dc.creator | Paunović, Verica | |
dc.creator | Ristić, Biljana | |
dc.creator | Bošnjak, Mihajlo | |
dc.creator | Zogović, Nevena | |
dc.creator | Mandić, Miloš | |
dc.creator | Tovilović-Kovačević, Gordana | |
dc.creator | Janjetović, Kristina | |
dc.creator | Trajković, Vladimir | |
dc.date.accessioned | 2022-01-17T12:05:37Z | |
dc.date.available | 2022-01-17T12:05:37Z | |
dc.date.issued | 2021 | |
dc.identifier.isbn | 978-86-919183-3-0 | |
dc.identifier.uri | https://www.sdir.ac.rs/apstrakti-SDIR-5/ | |
dc.identifier.uri | http://radar.ibiss.bg.ac.rs/handle/123456789/4709 | |
dc.description.abstract | Background: Intensive proliferation of tumor cells consumes a lot of energy. In nutrient deficiency substrates for energy metabolism are obtained by lysosomal degradation of unnecessary/dysfunctional intracellular organelles/molecules in the process of autophagy. Leakage of enlarged unstable lysosomes, which characterize tumor cells, causes cell death. We investigated antitumor effect of combined targeting of lysosomes/autophagy and energy metabolism. Material and Methods: Toxicity against U251 human glioma and B16 mouse melanoma cells was measured by viability tests. Type/mechanisms of cell death were determined by flow cytometry, immunoblot, fluorescent/electron microscopy and confirmed by appropriate genetic/pharmacological inhibitors. Therapeutic potential was estimated in B16 melanoma bearing C57Bl/6 mice. Results: In the first study, lysosomotropic autophagy inhibitor chloroquine (CQ) rapidly killed tumor cells incubated in the absence of serum. CQ-induced lysosomal destabilization triggered: oxidative stress, mitochondrial depolarization, and mixed apoptosis/necrosis of serum-deprived cells. In the second study, lysosomal detergent N-dodecylimidazole (NDI) synergized in antitumor activity with the glycolytic inhibitor 2-deoxy-D-glucose (2DG). NDI-triggered release of lysosomal enzymes into the cytoplasm caused mitochondrial damage and blocked oxidative phosphorylation, which synergized with 2DG-mediated glycolysis block in ATP reduction, oxidative stress, and necrosis. Interestingly, although both serum deprivation and 2DG stimulated autophagy, CQ- and NDI-induced autophagy suppression was irrelevant for their cytotoxicity. Importantly, CQ+food restriction and 2DG+NDI reduced melanoma growth in vivo. Conclusion: Autophagy independent antitumor effects of combined energy metabolism suppression and lysosomal destabilization might be exploited in cancer therapy. | sr |
dc.language.iso | en | sr |
dc.publisher | Beograd : Srpsko društvo istraživača raka | sr |
dc.rights | openAccess | sr |
dc.source | 5th Congress of the Serbian Association for Cancer Research – SDIR-5 with international participation „Translational potential of cancer research in Serbia“ | sr |
dc.subject | Autophagy | sr |
dc.subject | Combined Therapy | sr |
dc.subject | Energy Metabolism | sr |
dc.subject | Lysosomes | sr |
dc.title | Dual targeting of energy metabolism and lysosomes as an anticancer strategy; It is not all about autophagy | sr |
dc.type | conferenceObject | sr |
dc.rights.license | ARR | sr |
dc.rights.holder | © 2021 Srpsko društvo istraživača raka | sr |
dc.description.other | Đorđević Crnogorac M, Nedeljković M, editors. Abstract book: 5th Congress of the Serbian Association for Cancer Research with International Participation SDIR-5: Translational Potential of Cancer Research in Serbia; 2021 Dec 3; Virtual event. Beograd: Srpsko društvo istraživača raka; 2021. p. 8. | sr |
dc.citation.spage | 8 | |
dc.type.version | publishedVersion | sr |
dc.identifier.cobiss | 52655625 | |
dc.identifier.fulltext | https://radar.ibiss.bg.ac.rs/bitstream/id/9636/bitstream_9636.pdf | |
dc.citation.rank | M34 | |
dc.identifier.rcub | https://hdl.handle.net/21.15107/rcub_ibiss_4709 |