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dc.contributor.advisorGustafson, Daniel
dc.contributor.advisorMcGrath, Stephanie
dc.contributor.authorGross, Chase
dc.contributor.committeememberRegan, Daniel
dc.date.accessioned2021-01-11T11:20:10Z
dc.date.available2021-01-11T11:20:10Z
dc.date.issued2020
dc.description2020 Fall.
dc.descriptionIncludes bibliographical references.
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.publisherColorado State University. Libraries
dc.relation.ispartof2020- CSU Theses and Dissertations
dc.rightsCopyright of the original work is retained by the author.
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.dplaThe copyright and related rights status of this Item has not been evaluated (https://rightsstatements.org/vocab/CNE/1.0/). Please refer to the organization that has made the Item available for more information.
thesis.degree.disciplineClinical Sciences
thesis.degree.grantorColorado State University
thesis.degree.levelMasters
thesis.degree.nameMaster of Science (M.S.)


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