Potential of Novel Methyl Jasmonate Analogs as Anticancer Agents to Metabolically Target HK-2 Activity in Glioblastoma Cells

• DOI: 10.3389/fphar.2022.828400
• Publication Date: 2023-04-20T22:30:45Z
• Authors: Damla Uludağ; Sadık Bay; Bilgesu Onur Sucu; Özgecan Şavluğ İpek; Thomas Mohr; Mustafa Güzel; Nihal Karakaş
• Keywords: Pharmacology; autophagy; glioblastoma; apoptosis; 2DG; Apoptosis; hexokinase-II; RM1-950; Hexokinase-II; methyl jasmonate; 3. Good health; Necrosis; Methyl Jasmonate; Autophagy; Therapeutics. Pharmacology; Glioblastoma

Change in the energy metabolism of cancer cells, which display significant differences compared to normal is a rising phenomenon developing new therapeutic approaches against cancers. One metabolic enzymes, hexokinase-II (HK-II) involved glycolysis, and inhibiting HK-II activity may be potential target for therapy as most drugs clinical use act on DNA damage. Methyl jasmonate (MJ) one compounds blocking cells. In previous study, we showed that novel MJ analogs inhibit through VDAC detachment from mitochondria. this evaluate targeting HK-2 activity, patient cohort analysis, first determined expression levels prognostic significance highly lethal glioblastoma (GBM) brain tumor. We then examined vitro effects GBM Here, report that, among all, compound-10 (C-10) efficacy preclinical studies. Afterward, analyzed cell death triggered by C-10 two different lines. found treatment increased apoptotic/necrotic cells autophagy The newly developed analog, C-10, was activation authorities, mostly necrotic autophagic fashion at early stages treatment. Considering possibly decreased intracellular ATP mediated inhibition disabled interaction, more detailed analysis inhibition–mediated can provide deep understanding mechanism action oncosis/necroptosis axis. These findings an option design clinically relevant effective inhibitors suggest further study them anticancer agents GBM.