Skip to main content
Canna~Fangled Abstracts

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

By May 7, 2024May 21st, 2024No Comments

. 2024 May 7;41(6):140.

doi: 10.1007/s12032-024-02381-x.

Lei P Wang 1 2 3, Pablo Shimaoka Chagas 1 2 4, Évila Lopes Salles 1 2, Sahar Emami Naeini 1 2, Jules Gouron 1 2, Hannah M Rogers 1 2, Hesam Khodadadi 5, Bidhan Bhandari 1 2, Ahmet Alptekin 6, Xu Qin 7, Kumar Vaibhav 8, Vincenzo Costigliola 9, David C Hess 5, Krishnan M Dhandapani 8, Ali S Arbab 6, Martin J Rutkowski 8, Jack C Yu 10, Babak Baban 11 12 13 14
Affiliations 

Abstract

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-2α (eIF2α). 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 eIF2α expression and p-eIF2α 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.

Keywords: Biomolecular condensates, CBD, Cannabidiol, Glioblastoma, Integrated bioinformatics, Stress granules

PubMed Disclaimer

References

    1. Le Rhun E, Preusser M, Roth P, Reardon DA, van den Bent M, Wen P, Reifenberger G, Weller M. Molecular targeted therapy of glioblastoma. Cancer Treat Rev. 2019;80: 101896. https://doi.org/10.1016/j.ctrv.2019.101896 . – DOI – PubMed
    1. McKinnon C, Nandhabalan M, Murray SA, Plaha P. Glioblastoma: clinical presentation, diagnosis, and management. BMJ. 2021;374: n1560. https://doi.org/10.1136/bmj.n1560 . – DOI – PubMed
    1. Khodadadi H, Salles É, Alptekin A, Mehrabian D, Rutkowski M, Arbab AS, Yeudall WA, Yu JC, Morgan JC, Hess DC, et al. Inhalant cannabidiol inhibits glioblastoma progression through regulation of tumor microenvironment. Cannabis Cannabinoid Res. 2023;8:824–34. https://doi.org/10.1089/can.2021.0098 . – DOI – PubMed
    1. Jayabalan AK, Adivarahan S, Koppula A, Abraham R, Batish M, Zenklusen D, Griffin DE, Leung AKL. Stress granule formation, disassembly, and composition are regulated by alphavirus ADP-ribosylhydrolase activity. Proc Natl Acad Sci. 2021. https://doi.org/10.1073/pnas.2021719118 . – DOI – PubMed – PMC
    1. Swain P, Weber SC. Dissecting the complexity of biomolecular condensates. Biochem Soc Trans. 2020;48:2591–602. https://doi.org/10.1042/BST20200351 . – DOI – PubMed

MeSH terms

Substances

Leave a Reply