Multiomic Analysis Reveals Disruption of Cholesterol Homeostasis by Cannabidiol in Human Cell Lines

Guard, Steven E.; Chapnick, Douglas A.; Poss, Zachary C.; Ebmeier, Christopher C.; Jacobsen, Jeremy; Nemkov, Travis; Ball, Kerri A.; Webb, Kristofor J.; Simpson, Helen L.; Coleman, Stephen; Bunker, Eric; Ramirez, Adrian; Reisz, Julie A.; Sievers, Robert; Stowell, Michael H.B.; D’Alessandro, Angelo; Liu, Xuedong; Old, William M.

doi:10.1016/j.mcpro.2022.100262

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Multiomic Analysis Reveals Disruption of Cholesterol Homeostasis by Cannabidiol in Human Cell Lines

2022
By Guard, Steven E. ; Chapnick, Douglas A. ; Poss, Zachary C. ; ...
Source: Molecular & Cellular Proteomics, 21(10), 100262

[PDF-4.14 MB]

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Journal Title:

Molecular & Cellular Proteomics
Personal Author:

Guard, Steven E. ; Chapnick, Douglas A. ; Poss, Zachary C. ; Ebmeier, Christopher C. ; Jacobsen, Jeremy ; ... More +

Guard, Steven E. ; Chapnick, Douglas A. ; Poss, Zachary C. ; Ebmeier, Christopher C. ; Jacobsen, Jeremy ; Nemkov, Travis ; Ball, Kerri A. ; Webb, Kristofor J. ; Simpson, Helen L. ; Coleman, Stephen ; Bunker, Eric ; Ramirez, Adrian ; Reisz, Julie A. ; Sievers, Robert ; Stowell, Michael H.B. ; D’Alessandro, Angelo ; Liu, Xuedong ; Old, William M. Less -
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CIRES (Cooperative Institute for Research in Environmental Sciences)
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The nonpsychoactive cannabinoid, cannabidiol (CBD), is Food and Dug Administration approved for treatment of two drug-resistant epileptic disorders and is seeing increased use among the general public, yet the mechanisms that underlie its therapeutic effects and side-effect profiles remain unclear. Here, we report a systems-level analysis of CBD action in human cell lines using temporal multiomic profiling. FRET-based biosensor screening revealed that CBD elicits a sharp rise in cytosolic calcium, and activation of AMP-activated protein kinase in human keratinocyte and neuroblastoma cell lines. CBD treatment leads to alterations in the abundance of metabolites, mRNA transcripts, and proteins associated with activation of cholesterol biosynthesis, transport, and storage. We found that CBD rapidly incorporates into cellular membranes, alters cholesterol accessibility, and disrupts cholesterol-dependent membrane properties. Sustained treatment with high concentrations of CBD induces apoptosis in a dose-dependent manner. CBD-induced apoptosis is rescued by inhibition of cholesterol synthesis and potentiated by compounds that disrupt cholesterol trafficking and storage. Our data point to a pharmacological interaction of CBD with cholesterol homeostasis pathways, with potential implications in its therapeutic use.
Source:

Molecular & Cellular Proteomics, 21(10), 100262
DOI:

https://doi.org/10.1016/j.mcpro.2022.100262
ISSN:

1535-9476
Format:

pdf
Publisher:

Elsevier BV
Document Type:

Journal Article
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https://creativecommons.org/licenses/by/4.0/
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CC BY
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urn:sha-512:b8c9d28e28bd7092dc39185ce35185017e9b5ea6d1d94eb8d6d4fc1e6edc8b8a306e5c7ba4b26f824723a62295ac80d1a85a7f95d491136f49d0d14d75a8a0f7
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https://repository.library.noaa.gov/view/noaa/68398/noaa_68398_DS1.pdf
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Multiomic Analysis Reveals Disruption of Cholesterol Homeostasis by Cannabidiol in Human Cell Lines

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