P01.33.a Modulation of Autophagy and Anti-cancer Effects of the Hif-1α Inhibitor Kc7f2 in Glioma Cells
Year: 2025
Type: conference-abstract
Abstract: BACKGROUND Glioblastoma multiform, the most common and aggressive primary brain tumor, is characterized by a high degree of hypoxia and resistance to therapy because of its adaptation capacities, including autophagy and growth factors signaling. It is currently accepted that up-regulation of autophagy during hypoxia can favor tumor cell survival and growth. Autophagy, a conserved catabolic process implies engulfment of organelles and macromolecules into double-membrane vesicles termed autophagosomes, which merge with lysosomes to form the autophagolysosome. KC7F2 is cytotoxic against cancer cells under normoxic conditions and increases toxicity by rising HIF-1α levels under hypoxic conditions. We experimentally used KC7F2 active ingredient to target cancer metabolism. In present study, it was aimed to investigate the effects of treatment of glioma cells with KC7F2 and Temozolomid treatments on autophagy pathway. MATERIAL AND METHODS In our study, the apoptotic effect of KC7F2 and Temozolomid on U87MG cells was examined using the Annexin V method. Gene expression differences, particularly in autophagy-related genes, were determined by real-time qRT-PCR. RESULTS The cytotoxic effect of KC7F2 was assessed by calculating its IC₅₀ value, defined as the concentration required to reduce cell proliferation by 50%. The IC₅₀ values were determined as 22.99 μM at 24 hours, 19 μM at 48 hours, and 21.55 μM at 72 hours. In addition, KC7F2 treatment induced apoptosis in U87MG cells compared to the control group. As a result, After KC7F2 treatment, widespread suppression of ATG genes was observed: ATG10, ATG12, ATG16L1, ATG16L2, ATG3, ATG4B, ATG4C, ATG4D. Only ATG4A showed a slight increase. CONCLUSION In this regard, we suggest that this study will contribute to the standard glioblastoma treatment through regulating critical autophagy pathway-related genes.
Source: Neuro-Oncology
Authors: M Takanlou, L Takanlou, B Bilgin, M Yuncu, A Karadag, F Ozer, C Avci
Institutions: Ege University, İzmir Şehir Hastanesi
Language: English
Subfield: Epidemiology
Field: Medicine
Domain: Health Sciences
Open Access status: bronze
OpenAlex ID: W4414792425
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