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In Silico and In Vitro Analysis of Major Cannabis-Derived Compounds as Fatty Acid Amide Hydrolase Inhibitors
 
 
Article

Cannabis-Derived Compounds Cannabichromene and Δ9-Tetrahydrocannabinol Interact and Exhibit Cytotoxic Activity against Urothelial Cell Carcinoma Correlated with Inhibition of Cell Migration and Cytoskeleton Organization

1
Department of Urology, Sheba Medical Center, 52621 Ramat Gan, Israel
2
Institute of Plant Science, Agriculture Research Organization, Volcani Center, 7505101 Rishon LeZion, Israel
3
Israel Gene Bank, Agricultural Research Organization, Volcani Center, 7505101 Rishon LeZion, Israel
*
Author to whom correspondence should be addressed.
Academic Editors: Gioacchino Calapai and Dvora Namdar
Molecules 2021, 26(2), 465; https://doi.org/10.3390/molecules26020465
Received: 11 December 2020 / Revised: 8 January 2021 / Accepted: 12 January 2021 / Published: 17 January 2021
(This article belongs to the Special Issue Pharmaceutical Drugs Based on Cannabis)
Cannabis sativa contains more than 500 constituents, yet the anticancer properties of the vast majority of cannabis compounds remains unknown. We aimed to identify cannabis compounds and their combinations presenting cytotoxicity against bladder urothelial carcinoma (UC), the most common urinary system cancer. An XTT assay was used to determine cytotoxic activity of C. sativa extracts on T24 and HBT-9 cell lines. Extract chemical content was identified by high-performance liquid chromatography (HPLC). Fluorescence-activated cell sorting (FACS) was used to determine apoptosis and cell cycle, using stained F-actin and nuclei. Scratch and transwell assays were used to determine cell migration and invasion, respectively. Gene expression was determined by quantitative Polymerase chain reaction (PCR). The most active decarboxylated extract fraction (F7) of high-cannabidiol (CBD) C. sativa was found to contain cannabichromene (CBC) and Δ9-tetrahydrocannabinol (THC). Synergistic interaction was demonstrated between CBC + THC whereas cannabinoid receptor (CB) type 1 and type 2 inverse agonists reduced cytotoxic activity. Treatments with CBC + THC or CBD led to cell cycle arrest and cell apoptosis. CBC + THC or CBD treatments inhibited cell migration and affected F-actin integrity. Identification of active plant ingredients (API) from cannabis that induce apoptosis and affect cell migration in UC cell lines forms a basis for pre-clinical trials for UC treatment. View Full-Text
Keywords: apoptosis; cannabis; cannabinoids; cancer; F-actin; urothelial carcinoma apoptosis; cannabis; cannabinoids; cancer; F-actin; urothelial carcinoma
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MDPI and ACS Style

Anis, O.; Vinayaka, A.C.; Shalev, N.; Namdar, D.; Nadarajan, S.; Anil, S.M.; Cohen, O.; Belausov, E.; Ramon, J.; Mayzlish Gati, E.; Koltai, H. Cannabis-Derived Compounds Cannabichromene and Δ9-Tetrahydrocannabinol Interact and Exhibit Cytotoxic Activity against Urothelial Cell Carcinoma Correlated with Inhibition of Cell Migration and Cytoskeleton Organization. Molecules 2021, 26, 465. https://doi.org/10.3390/molecules26020465

AMA Style

Anis O, Vinayaka AC, Shalev N, Namdar D, Nadarajan S, Anil SM, Cohen O, Belausov E, Ramon J, Mayzlish Gati E, Koltai H. Cannabis-Derived Compounds Cannabichromene and Δ9-Tetrahydrocannabinol Interact and Exhibit Cytotoxic Activity against Urothelial Cell Carcinoma Correlated with Inhibition of Cell Migration and Cytoskeleton Organization. Molecules. 2021; 26(2):465. https://doi.org/10.3390/molecules26020465

Chicago/Turabian Style

Anis, Omer, Ajjampura C. Vinayaka, Nurit Shalev, Dvora Namdar, Stalin Nadarajan, Seegehalli M. Anil, Ofer Cohen, Eduard Belausov, Jacob Ramon, Einav Mayzlish Gati, and Hinanit Koltai. 2021. "Cannabis-Derived Compounds Cannabichromene and Δ9-Tetrahydrocannabinol Interact and Exhibit Cytotoxic Activity against Urothelial Cell Carcinoma Correlated with Inhibition of Cell Migration and Cytoskeleton Organization" Molecules 26, no. 2: 465. https://doi.org/10.3390/molecules26020465

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