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Open AccessArticle

Cytotoxic Effects of Cannabinoids on Human HT-29 Colorectal Adenocarcinoma Cells: Different Mechanisms of THC, CBD, and CB83

1
Department of Medical and Surgical Sciences and Neurosciences, University of Siena, 53100 Siena, Italy
2
Department of Molecular and Developmental Medicine, University of Siena, 53100 Siena, Italy
3
Department of Biotechnology, Chemistry and Pharmacy, University of Siena, 53100 Siena, Italy
4
Department of Business and Law, University of Siena, 53100 Siena, Italy
*
Author to whom correspondence should be addressed.
Int. J. Mol. Sci. 2020, 21(15), 5533; https://doi.org/10.3390/ijms21155533
Received: 15 July 2020 / Revised: 29 July 2020 / Accepted: 30 July 2020 / Published: 1 August 2020
(This article belongs to the Section Molecular Pharmacology)
In this study, we investigated the effects of exposition to IC50 dose for 24 h of a new synthetic cannabinoid (CB83) and of phytocannabinoids Δ9-tetrahydrocannabinol (THC) and cannabidiol (CBD) on HT-29 colorectal carcinoma cells. Cell viability and proliferative activity evaluated using the MTT, lactate dehydrogenase (LDH), and CyQUANT assays showed that cell viability was significantly affected when CB83, THC, and CBD were administered to cells. The results obtained showed that the reduced glutathione/oxidized glutathione ratio was significantly reduced in the cells exposed to CBD and significantly increased in the cells treated with the CB83 when compared to the controls. CBD treatment causes a significant increase in malondialdehyde content. The catalase activity was significantly reduced in HT-29 cells after incubation with CB83, THC, and CBD. The activities of glutathione reductase and glutathione peroxidase were significantly increased in cells exposed to THC and significantly decreased in those treated with CBD. The ascorbic acid content was significantly reduced in cells exposed to CB83, THC, and CBD. The ultrastructural investigation by TEM highlighted a significantly increased percentage of cells apoptotic and necrotic after CB83 exposition. The Annexin V-Propidium Iodide assay showed a significantly increased percentage of cells apoptotic after CB83 exposition and necrotic cells after CBD and THC exposition. Our results proved that only CBD induced oxidative stress in HT-29 colorectal carcinoma cells via CB receptor-independent mechanisms and that CB83 caused a mainly CB2 receptor-mediated antiproliferative effect comparable to 5-Fuorouracil, which is still the mainstay drug in protocols for colorectal cancer. View Full-Text
Keywords: HT-29 cells; synthetic cannabinoid; Δ9-tetrahydrocannabinol; cannabidiol; oxidative stress; apoptosis HT-29 cells; synthetic cannabinoid; Δ9-tetrahydrocannabinol; cannabidiol; oxidative stress; apoptosis
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MDPI and ACS Style

Cerretani, D.; Collodel, G.; Brizzi, A.; Fiaschi, A.I.; Menchiari, A.; Moretti, E.; Moltoni, L.; Micheli, L. Cytotoxic Effects of Cannabinoids on Human HT-29 Colorectal Adenocarcinoma Cells: Different Mechanisms of THC, CBD, and CB83. Int. J. Mol. Sci. 2020, 21, 5533.

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