Cannabidiol induces autophagy via ERK1/2 activation in neural cells

Vrechi, Talita A M; Leão, Anderson H.F.F.; Morais, Ingrid B M; Abı́lio, Vanessa C.; Zuardi, Antônio Waldo; Hallak, Jaime Eduardo Cecílio; Crippa, José Alexandre S; Bincoletto, Cláudia; Ureshino, Rodrigo Portes; Smaili, Soraya Soubhi; Pereira, Gustavo José da Silva

doi:10.1038/s41598-021-84879-2

Cited by 39 publications

(28 citation statements)

References 84 publications

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“…Their findings suggest a novel TRPV4-CBD-mitophagy pathway in glioma and combination of CBD and TMZ as a potential to explore in future clinical studies. Additionally, Vrechi and colleagues show CBD stimulates autophagy signal transduction via crosstalk of ERK1/2 and AKT kinases and that CBD-induced autophagy was reduced in presence of CB receptors and TRPV1 receptor antagonists, AM251, AM630 and capsazepine in neuroblastoma and murine astrocyte cell lines (Vrechi et al 2021 ).…”

Section: Resultsmentioning

confidence: 99%

Cannabinoids in the landscape of cancer

Mangal

Erridge

Habib

et al. 2021

J Cancer Res Clin Oncol

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Introduction Cannabinoids are a group of terpenophenolic compounds derived from the Cannabis sativa L. plant. There is a growing body of evidence from cell culture and animal studies in support of cannabinoids possessing anticancer properties. Method A database search of peer reviewed articles published in English as full texts between January 1970 and April 2021 in Google Scholar, MEDLINE, PubMed and Web of Science was undertaken. References of relevant literature were searched to identify additional studies to construct a narrative literature review of oncological effects of cannabinoids in pre-clinical and clinical studies in various cancer types. Results Phyto-, endogenous and synthetic cannabinoids demonstrated antitumour effects both in vitro and in vivo. However, these effects are dependent on cancer type, the concentration and preparation of the cannabinoid and the abundance of receptor targets. The mechanism of action of synthetic cannabinoids, (−)-trans-Δ9-tetrahydrocannabinol (Δ9-THC) and cannabidiol (CBD) has mainly been described via the traditional cannabinoid receptors; CB1 and CB2, but reports have also indicated evidence of activity through GPR55, TRPM8 and other ion channels including TRPA1, TRPV1 and TRPV2. Conclusion Cannabinoids have shown to be efficacious both as a single agent and in combination with antineoplastic drugs. These effects have occurred through various receptors and ligands and modulation of signalling pathways involved in hallmarks of cancer pathology. There is a need for further studies to characterise its mode of action at the molecular level and to delineate efficacious dosage and route of administration in addition to synergistic regimes.

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Section: Resultsmentioning

confidence: 99%

Cannabinoids in the landscape of cancer

Mangal

Erridge

Habib

et al. 2021

J Cancer Res Clin Oncol

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“…Autophagy is also essential during cartilage differentiation, which also requires calcium, of human umbilical cord mesenchymal stem cells (hUCMSCs) [83]. Research showed that GSK3 positively regulated the mammalian target of rapamycin complex 1 (mTORC1) to suppress autophagic activity, whereas the GSK3β inhibitor prevented the progression of LC3-II/LC3-I.…”

Section: Autophagy/apoptosis and Stem Cell Functionmentioning

confidence: 99%

Calcium Signaling Regulates Autophagy and Apoptosis

Sukumaran

Conceicao

Sun

et al. 2021

Cells

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Calcium (Ca2+) functions as a second messenger that is critical in regulating fundamental physiological functions such as cell growth/development, cell survival, neuronal development and/or the maintenance of cellular functions. The coordination among various proteins/pumps/Ca2+ channels and Ca2+ storage in various organelles is critical in maintaining cytosolic Ca2+ levels that provide the spatial resolution needed for cellular homeostasis. An important regulatory aspect of Ca2+ homeostasis is a store operated Ca2+ entry (SOCE) mechanism that is activated by the depletion of Ca2+ from internal ER stores and has gained much attention for influencing functions in both excitable and non-excitable cells. Ca2+ has been shown to regulate opposing functions such as autophagy, that promote cell survival; on the other hand, Ca2+ also regulates programmed cell death processes such as apoptosis. The functional significance of the TRP/Orai channels has been elaborately studied; however, information on how they can modulate opposing functions and modulate function in excitable and non-excitable cells is limited. Importantly, perturbations in SOCE have been implicated in a spectrum of pathological neurodegenerative conditions. The critical role of autophagy machinery in the pathogenesis of neurodegenerative diseases such as Alzheimer’s, Parkinson’s, and Huntington’s diseases, would presumably unveil avenues for plausible therapeutic interventions for these diseases. We thus review the role of SOCE-regulated Ca2+ signaling in modulating these diverse functions in stem cell, immune regulation and neuromodulation.

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“…Along these lines, a recent publication showed that CBD induces autophagy in a concentration-dependent manner that requires crosstalk between the extracellular signal-regulated protein kinases 1 and 2 (ERK1/2) and AKT, also known as protein kinase B (PKB). These signaling pathways are essential for control proliferation, cell survival and growth [ 97 ].…”

Section: Discussionmentioning

confidence: 99%

Cannabinoids Reduce Extracellular Vesicle Release from HIV-1 Infected Myeloid Cells and Inhibit Viral Transcription

DeMarino

Cowen

Khatkar

et al. 2022

Cells

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Of the 37.9 million individuals infected with human immunodeficiency virus type 1 (HIV-1), approximately 50% exhibit HIV-associated neurocognitive disorders (HAND). We and others previously showed that HIV-1 viral RNAs, such as trans-activating response (TAR) RNA, are incorporated into extracellular vesicles (EVs) and elicit an inflammatory response in recipient naïve cells. Cannabidiol (CBD) and Δ9-tetrahydrocannabinol (THC), the primary cannabinoids present in cannabis, are effective in reducing inflammation. Studies show that cannabis use in people living with HIV-1 is associated with lower viral load, lower circulating CD16+ monocytes and high CD4+ T-cell counts, suggesting a potentially therapeutic application. Here, HIV-1 infected U1 monocytes and primary macrophages were used to assess the effects of CBD. Post-CBD treatment, EV concentrations were analyzed using nanoparticle tracking analysis. Changes in intracellular and EV-associated viral RNA were quantified using RT-qPCR, and changes in viral proteins, EV markers, and autophagy proteins were assessed by Western blot. Our data suggest that CBD significantly reduces the number of EVs released from infected cells and that this may be mediated by reducing viral transcription and autophagy activation. Therefore, CBD may exert a protective effect by alleviating the pathogenic effects of EVs in HIV-1 and CNS-related infections.

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Cannabidiol induces autophagy via ERK1/2 activation in neural cells

Cited by 39 publications

References 84 publications

Cannabinoids in the landscape of cancer

Cannabinoids in the landscape of cancer

Calcium Signaling Regulates Autophagy and Apoptosis

Cannabinoids Reduce Extracellular Vesicle Release from HIV-1 Infected Myeloid Cells and Inhibit Viral Transcription

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