Anti-proliferative and cytotoxic effects of CBD and CBDA in human colorectal cancer
Publication Date
July 19, 2019
Creator
Abstract
Introduction:
Colorectal cancer (CRC) is one of the most prevalent cancers in Europe and fourth most common globally (Boyle and Langman, 2000). The phytocannabinoids, cannabidiol (CBD) and cannabidiolic acid (CBDA) are non-psychoactive cannabis derived lipid compounds which are being increasingly investigated for their anti-cancer effects. CBD and CBDA have proven beneficial in multiple in vitro human cancer cell lines exhibiting anti-inflammatory, anti-proliferative and cytotoxic effects. We aimed to explore the potential application of these compounds and their effects in a CRC cell and human explant tumour model.
Methods:
Exploration of the anti-proliferative and cytotoxic properties of CBD and CBDA was conducted in a CaCo-2 human colorectal carcinoma cell line followed by a CRC explant model using human tissue. Metabolic activity was quantified using the resazurin salt assay over 72 hours. Interleukin expression was analysed by enzyme-linked immunosorbent assay. A BCA assay was used for the analysis of total protein content and lactate dehydrogenase used as a method of assessing cell viability. Receptor antagonists were used to explore the mechanisms of the anti-proliferative and cytotoxic effects. Cytokine and protein responses were measured through enzyme linked immunosorbent assaying (ELISA).
Results:
We report significant anti-proliferative and cytotoxic effects in CaCo-2 cells at a concentration of 70µM in proliferating cells and 50 µM in confluent cells. CBDA exhibited higher anti-proliferative potency than CBD exerting effects at 30µM but demonstrated only weak cytotoxic effects. CBDA and CBD increased extracellular LDH and decreased total protein content of CaCo-2 cells indicating cytotoxicity. Combination treatments of CBD and CBDA exhibited no increase in efficacy. Our explant model exhibited several promising anti-cancer effects, however these studies comprised of only an n=2 due to time constraints and delays. The GPR55, 5-HT1A PPARδ receptors were implicated in the mediation of CBD and CBDA’s anti-proliferative and cytotoxic effects.
Conclusions:
CBD and CBDA show great efficacy as anti-cancer compounds. We show that the anti-proliferative and cytotoxic effects appear to be mediated in a GPR55, 5-HT1A PPARδ sensitive manner. For the first time, we demonstrate that CBDA appears to be a more potent anti-proliferative whilst CBD exhibits higher cell cytotoxicity. Combination treatments of CBD and CBDA exhibit no augmentation in effect.
Item Type
ethesis
Thesis Type
MRes
Supervisors
Subjects (LC)
Associated Schools / Departments
Division of Medical Sciences and Graduate Entry Medicine
School of Health Sciences
eprints ID
56784
UoN Repository URI
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CBD and CBDA in the treatment of Colorectal cancer .pdf
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Full-text
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