NEW CHALCONE COMPOUND EXHIBITS MICRORNA-MEDIATED ANTICANCER PROPERTIES IN GLIOBLASTOMA

Denis Mustafov, Shoib Siddiqui, Irshad Ahmad, Shagufta Waseem, Jim Gkantalis, Patricia Garcia, Maria Braoudaki

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Abstract

Therapy-resistant glioblastoma (GB) constitutes the most lethal adult brain malignancy, bearing extremely poor patients’ prognosis. Combinational therapies often come with severe side effects and significant financial costs, highlighting the urgent need for alternative, low-toxicity treatments. This study sought to investigate the therapeutic efficacy of a novel synthetic chalcone, SHG-44, and its cellular mechanistic actions in U87MG and U251 glioblastoma cell line models. In vitro, cell viability assays demonstrated that SHG-44 significantly reduced cell viability in GB cells, with an IC50 of 70.39μΜ and 64.19μΜ within U87MG and U251MG cells, respectively. In line with these findings, a colony formation assay revealed a significant impairment of GB cells' clonogenic survival. SHG-44 effects on cell migration demonstrated a significant impairment in cell migration at 100μΜ SHG-44 within both GB cell lines. Reactive oxygen species (ROS) assay showed a significant increase of ROS at 40μΜ SHG-44 concentrations within U87MG cells and non-significant elevation of ROS within U251MG cells. DAPI and acridine orange/ethidium bromide staining demonstrated that SHG-44 mediated cytotoxicity in U87MG and U251MG through apoptosis induction. Small RNA-sequencing analysis demonstrated that SHG-44 could regulate various cellular pathways through microRNA expression modulation in glioblastoma cell models. Further in-silico analysis of the pharmacokinetics and pharmacodynamics prostrates of SHG-44 demonstrated that the compound possessed sufficient absorption, distribution, potential to pass through the blood brain barrier, and low oral toxicity characterises. Taken together these findings suggested the potential anti-cancer properties of the newly synthesised chalcone compound, SHG-44 and its potential implications in GB therapeutic management. New chalcone compound exibits microRNA-mediated anticancer properties in glioblastoma
Original languageEnglish
JournalClinical Pharmacology & Therapeutics
Publication statusSubmitted - 4 Jul 2024

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