Potential of novel methyl jasmonate analogs as anticancer agents to metabolically target HK-2 activity in glioblastoma cells

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dc.authorid0000-0001-8089-1330
dc.authorid0000-0003-0957-6965
dc.authorid0000-0003-1827-9540
dc.authorid0000-0002-1423-0435
dc.authorid0000-0002-9096-1512
dc.contributor.authorUludağ, Damla
dc.contributor.authorBay, Sadık
dc.contributor.authorOnur Sucu, Bilgesu
dc.contributor.authorŞavluğ İpek, Özgecan
dc.contributor.authorMohr, Thomas
dc.contributor.authorGüzel, Mustafa
dc.contributor.authorKarakaş, Nihal
dc.date.accessioned2022-06-23T11:39:44Z
dc.date.available2022-06-23T11:39:44Z
dc.date.issued2022
dc.departmentİstanbul Medipol Üniversitesi, Rektörlük, Sağlık Bilim ve Teknolojileri Araştırma Enstitüsü
dc.departmentİstanbul Medipol Üniversitesi, Rektörlük, Rejeneratif ve Restoratif Tıp Araştırmaları Merkezi (REMER)
dc.departmentİstanbul Medipol Üniversitesi, Sağlık Hizmetleri Meslek Yüksekokulu, Tıbbi Laboratuvar Teknikleri Ana Bilim Dalı
dc.departmentİstanbul Medipol Üniversitesi, Uluslararası Tıp Fakültesi, Dahili Tıp Bilimleri Bölümü, Tıbbi Farmakoloji Ana Bilim Dalı
dc.departmentİstanbul Medipol Üniversitesi, Tıp Fakültesi, Temel Tıp Bilimleri Bölümü, Tıbbi Biyoloji Ana Bilim Dalı
dc.description.abstractChange in the energy metabolism of cancer cells, which display significant differences compared to normal cells, is a rising phenomenon in developing new therapeutic approaches against cancers. One of the metabolic enzymes, hexokinase-II (HK-II) is involved in glycolysis, and inhibiting the HK-II activity may be a potential metabolic target for cancer therapy as most of the drugs in clinical use act on DNA damage. Methyl jasmonate (MJ) is one of the compounds blocking HK-II activity in cancer cells. In a previous study, we showed that the novel MJ analogs inhibit HK-II activity through VDAC detachment from the mitochondria. In this study, to evaluate the potential of targeting HK-2 activity, through patient cohort analysis, we first determined HK-2 expression levels and prognostic significance in highly lethal glioblastoma (GBM) brain tumor. We then examined the in vitro therapeutic effects of the novel analogs in the GBM cells. Here, we report that, among all, compound-10 (C-10) showed significant in vitro therapeutic efficacy as compared to MJ which is in use for preclinical and clinical studies. Afterward, we analyzed cell death triggered by C-10 in two different GBM cell lines. We found that C-10 treatment increased the apoptotic/necrotic cells and autophagy in GBM cells. The newly developed analog, C-10, was found to be lethal against GBM by the activation of cell death authorities, mostly in a necrotic and autophagic fashion at the early stages of the treatment. Considering that possibly decreased intracellular ATP levels by C-10 mediated inhibition of HK-2 activity and disabled VDAC interaction, a more detailed analysis of HK-2 inhibition-mediated cell death can provide a deep understanding of the mechanism of action on the oncosis/necroptosis axis. These findings provide an option to design clinically relevant and effective novel HK-II inhibitors and suggest novel MJ analogs to further study them as potential anticancer agents against GBM.
dc.description.sponsorshipEuropean Cooperation in Science and Technology (COST)en_US
dc.identifier.citationUludağ, D., Bay, S., Onur Sucu, B., Şavluğ İpek, Ö., Mohr, T., Güzel, M. ... Karakaş, N. (2022). Potential of novel methyl jasmonate analogs as anticancer agents to metabolically target HK-2 activity in glioblastoma cells. Frontiers in Pharmacology, 13. http://doi.org/10.3389/fphar.2022.828400
dc.identifier.doi10.3389/fphar.2022.828400
dc.identifier.issn1663-9812
dc.identifier.pmid35677429
dc.identifier.scopus2-s2.0-85131799768
dc.identifier.scopusqualityQ1
dc.identifier.urihttp://doi.org/10.3389/fphar.2022.828400
dc.identifier.urihttps://hdl.handle.net/20.500.12511/9531
dc.identifier.volume13
dc.identifier.wos000807209300001en_US
dc.identifier.wosqualityQ1
dc.indekslendigikaynakWeb of Science
dc.indekslendigikaynakScopus
dc.indekslendigikaynakPubMed
dc.institutionauthorUludağ, Damla
dc.institutionauthorBay, Sadık
dc.institutionauthorOnur Sucu, Bilgesu
dc.institutionauthorŞavluğ İpek, Özgecan
dc.institutionauthorGüzel, Mustafa
dc.institutionauthorKarakaş, Nihal
dc.language.isoen
dc.publisherFrontiers Media S.A.
dc.relation.ispartofFrontiers in Pharmacologyen_US
dc.relation.publicationcategoryMakale - Uluslararası Hakemli Dergi - Kurum Öğretim Elemanı
dc.rightsAttribution 4.0 International*
dc.rightsinfo:eu-repo/semantics/openAccess
dc.rights.urihttps://creativecommons.org/licenses/by/4.0/*
dc.subjectHexokinase-II
dc.subjectMethyl Jasmonate
dc.subject2DG
dc.subjectGlioblastoma
dc.subjectApoptosis
dc.subjectAutophagy
dc.subjectNecrosis
dc.titlePotential of novel methyl jasmonate analogs as anticancer agents to metabolically target HK-2 activity in glioblastoma cells
dc.typeArticle

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