Cepharanthine induces ROS stress in glioma and neuronal cells via modulation of VDAC permeability
العنوان: | Cepharanthine induces ROS stress in glioma and neuronal cells via modulation of VDAC permeability |
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المؤلفون: | Joanna Rossowska, Anna Szewczyk, Mounir Tarek, Jolanta Saczko, Wojciech Szlasa, Karolina Cierluk, Julita Kulbacka |
المساهمون: | Wroclaw University of Science and Technology, Wroclaw Medical University [Wrocław, Pologne], Polish Academy of Sciences (PAN), Laboratoire de Physique et Chimie Théoriques (LPCT), Institut de Chimie du CNRS (INC)-Université de Lorraine (UL)-Centre National de la Recherche Scientifique (CNRS) |
المصدر: | Saudi Pharmaceutical Journal Saudi Pharmaceutical Journal, Elsevier, 2020, 28 (11), pp.1364-1373. ⟨10.1016/j.jsps.2020.08.026⟩ Saudi Pharmaceutical Journal : SPJ Saudi Pharmaceutical Journal, Vol 28, Iss 11, Pp 1364-1373 (2020) |
بيانات النشر: | HAL CCSD, 2020. |
سنة النشر: | 2020 |
مصطلحات موضوعية: | 0301 basic medicine, Voltage-dependent anion channel, Pharmaceutical Science, Mitochondrion, 03 medical and health sciences, chemistry.chemical_compound, 0302 clinical medicine, Cepharanthine, MTT assay, Cytotoxicity, ComputingMethodologies_COMPUTERGRAPHICS, Pharmacology, chemistry.chemical_classification, Reactive oxygen species, VDAC, biology, [SDV.BBM.BS]Life Sciences [q-bio]/Biochemistry, Molecular Biology/Structural Biology [q-bio.BM], Calcium channel, lcsh:RM1-950, ROS, Glioma, 3. Good health, [SDV.BBM.BP]Life Sciences [q-bio]/Biochemistry, Molecular Biology/Biophysics, [CHIM.THEO]Chemical Sciences/Theoretical and/or physical chemistry, lcsh:Therapeutics. Pharmacology, 030104 developmental biology, chemistry, Apoptosis, 030220 oncology & carcinogenesis, Neuronal cells, biology.protein, Biophysics, Original Article |
الوصف: | Graphical abstract Cepharanthine (CEP) is a bisbenzylisoquinoline alkaloid. Molecular dynamics studies show that CEP interacts with Voltage-dependent anion channel (VDAC), inducing the voltage-independent channel narrowing. In the new conformation, transport between mitochondria and cytoplasm is altered, which leads to the dose-dependent cytotoxicity. The biological effects of the interaction were investigated on glioblastoma multiforme (SNB-19) and neuronal (PC-12 + NGF) cell lines. The cytotoxic potential of cepharanthine was determined by MTT assay and flow cytometry apoptosis/necrosis studies. T-type calcium channel and VDAC were labelled by the immunocytochemical method. Additionally, fluorescent labelling of reactive oxygen species and mitochondria was performed. Changes in the pore size of VDAC were calculated as well. Molecular dynamics simulations were carried out to examine the interactions of cepharanthine with VDAC. The obtained results prove that cepharanthine enhances the apoptosis in glioma and neuronal cells by the release of reactive oxygen species. Cepharanthine alters the mitochondria-to-cytoplasm transport and thus induces the cytotoxicity with no selectivity. |
اللغة: | English |
تدمد: | 1319-0164 |
DOI: | 10.1016/j.jsps.2020.08.026⟩ |
URL الوصول: | https://explore.openaire.eu/search/publication?articleId=doi_dedup___::569dce7ea1e1015363a73281450e6fb1 https://hal.univ-lorraine.fr/hal-03096148/file/1-s2.0-S1319016420302061-main.pdf |
Rights: | OPEN |
رقم الانضمام: | edsair.doi.dedup.....569dce7ea1e1015363a73281450e6fb1 |
قاعدة البيانات: | OpenAIRE |
تدمد: | 13190164 |
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DOI: | 10.1016/j.jsps.2020.08.026⟩ |