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Cannabidiol induces apoptosis and perturbs mitochondrial function in canine and human glioma cells

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dc.contributor.authorGross, Chase, author
dc.contributor.authorGustafson, Daniel, advisor
dc.contributor.authorMcGrath, Stephanie, advisor
dc.contributor.authorRegan, Daniel, committee member
dc.date.accessioned2021-01-11T11:20:10Z
dc.date.available2021-01-11T11:20:10Z
dc.date.issued2020
dc.description.abstractCannabidiol (CBD), the major non-psychoactive compound found in cannabis, is frequently used both as a nutraceutical and therapeutic. Clinical studies suggest CBD may be beneficial for treating rare forms of epilepsy and inflammatory conditions but despite anecdotal evidence as an anticancer agent, little is known about the effect it has on cancer cells. Given the intractability and poor prognoses of brain cancers in both human and veterinary medicine, we characterized the in vitro cytotoxicity of CBD on human and canine gliomas. Glioma cells treated with CBD showed a range of cytotoxicity from 4.9-8.2 μg/mL; canine cells appeared to be more sensitive than human. Treatment with >5 μg/mL CBD invariably produced large cytosolic vesicles. Next, the mode of cell death was interrogated using pharmacologic inhibitors. Inhibition of apoptosis was sufficient to rescue CBD-mediated cytotoxicity. Inhibition of RIPK3, a classical necroptosis protein, rescued cells from death and prevented the formation of the large cytosolic vesicles. Analysis of cell death by resazurin reduction showed much higher sensitivity than other cytotoxicity methods and suggested disruption of the mitochondria. Cellular mitochondrial activity in the presence of CBD was assessed and within two hours of treatment CBD reduced oxygen consumption in a dose dependent manner with almost complete ablation of activity at 10 μg/mL CBD. Fluorescent imaging with a mitochondrial-specific dye revealed that the large cytosolic vesicles were, in fact, swollen mitochondria. Lastly, calcium channels were inhibited and the effect on cell death was measured. Inhibition of mitochondrial channel VDAC1, but not the TRPV1 channel, rescued cells from CBD-mediated cytotoxicity. These results demonstrate the cytotoxic nature of CBD in human and canine glioma cells and suggest a mechanism of action involving dysregulation of calcium homeostasis and mitochondrial activity.
dc.format.mediumborn digital
dc.format.mediummasters theses
dc.identifierGross_colostate_0053N_16312.pdf
dc.identifier.urihttps://hdl.handle.net/10217/219526
dc.languageEnglish
dc.language.isoeng
dc.publisherColorado State University. Libraries
dc.relation.ispartof2020-
dc.rightsCopyright and other restrictions may apply. User is responsible for compliance with all applicable laws. For information about copyright law, please see https://libguides.colostate.edu/copyright.
dc.subjectcancer
dc.subjectglioma
dc.subjecttranslational
dc.subjectcannabidiol
dc.subjectapoptosis
dc.subjectmitochondria
dc.titleCannabidiol induces apoptosis and perturbs mitochondrial function in canine and human glioma cells
dc.typeText
dcterms.rights.dplaThis Item is protected by copyright and/or related rights (https://rightsstatements.org/vocab/InC/1.0/). You are free to use this Item in any way that is permitted by the copyright and related rights legislation that applies to your use. For other uses you need to obtain permission from the rights-holder(s).
thesis.degree.disciplineClinical Sciences
thesis.degree.grantorColorado State University
thesis.degree.levelMasters
thesis.degree.nameMaster of Science (M.S.)

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