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Altering biomolecular condensates as a potential mechanism that mediates cannabidiol effect on glioblastoma

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单位: [1]Augusta Univ, DCG Ctr Excellence Res Scholarship & Innovat CERSI, Augusta, GA 30912 USA [2]Augusta Univ, Dent Coll Georgia, Dept Oral Biol & Diagnost Sci, Augusta, GA 30912 USA [3]Med Cannabis Georgia LLC, Georgia Inst Cannabis Res, Augusta, GA 30912 USA [4]Univ Sao Paulo, Sch Pharmaceut Sci, Dept Clin Anal Toxicol & Food Sci, Ribeirao Preto, SP, Brazil [5]Augusta Univ, Med Coll Georgia, Dept Neurol, Augusta, GA 30912 USA [6]Augusta Univ, Georgia Canc Ctr, Augusta, GA USA [7]Huazhong Univ Sci & Technol,Tongji Hosp,Tongji Med Coll,Canc Biol Res Ctr,Wuhan,Peoples R China [8]Huazhong Univ Sci & Technol,Tongji Hosp,Tongji Med Coll,Dept Stomatol,Wuhan,Peoples R China [9]Augusta Univ, Med Coll Georgia, Dept Neurosurg, Augusta, GA 30912 USA [10]European Med Assoc EMA, Brussels, Belgium [11]Augusta Univ, Med Coll Georgia, Dept Surg, Augusta, GA 30912 USA
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关键词: Glioblastoma CBD Cannabidiol Biomolecular condensates Stress granules Integrated bioinformatics

摘要:
Glioblastoma (GBM) is an extremely aggressive primary brain tumor with poor prognosis, short survival time post-diagnosis and high recurrence. Currently, no cure for GBM exists. The identification of an effective therapeutic modality for GBM remains a high priority amongst medical professionals and researches. In recent studies, inhalant cannabidiol (CBD) has demonstrated promise in effectively inhibiting GBM tumor growth. However, exactly how CBD treatment affects the physiology of these tumor cells remains unclear. Stress granules (SG) (a sub-class of biomolecular condensates (BMC)) are dynamic, membrane-less intracellular microstructures which contain proteins and nucleic acids. The formation and signaling of SGs and BMCs plays a significant role in regulating malignancies. This study investigates whether inhaled CBD may play an intervening role towards SGs in GBM tumor cells. Integrated bioinformatics approaches were preformed to gain further insights. This includes use of Immunohistochemistry and flow cytometry to measure SGs, as well as expression and phosphorylation of eukaryotic initiation factor-2 alpha (eIF2 alpha). The findings of this study reveal that CBD receptors (and co-regulated genes) have the potential to play an important biological role in the formation of BMCs within GBM. In this experiment, CBD treatment significantly increased the volume of TIAR-1. This increase directly correlated with elevation in both eIF2 alpha expression and p-eIF2 alpha in CBD treated tissues in comparison to the placebo group (p < 0.05). These results suggest that inhalant CBD significantly up-regulated SGs in GBM, and thus support a theory of targeting BMCs as a potential therapeutic substrate for treating GBM.

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出版当年[2023]版:
大类 | 4 区 医学
小类 | 4 区 肿瘤学
最新[2025]版:
大类 | 4 区 医学
小类 | 4 区 肿瘤学
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Q3 ONCOLOGY
最新[2023]版:
Q2 ONCOLOGY

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第一作者单位: [1]Augusta Univ, DCG Ctr Excellence Res Scholarship & Innovat CERSI, Augusta, GA 30912 USA [2]Augusta Univ, Dent Coll Georgia, Dept Oral Biol & Diagnost Sci, Augusta, GA 30912 USA [3]Med Cannabis Georgia LLC, Georgia Inst Cannabis Res, Augusta, GA 30912 USA
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通讯机构: [1]Augusta Univ, DCG Ctr Excellence Res Scholarship & Innovat CERSI, Augusta, GA 30912 USA [2]Augusta Univ, Dent Coll Georgia, Dept Oral Biol & Diagnost Sci, Augusta, GA 30912 USA [3]Med Cannabis Georgia LLC, Georgia Inst Cannabis Res, Augusta, GA 30912 USA [5]Augusta Univ, Med Coll Georgia, Dept Neurol, Augusta, GA 30912 USA
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