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

Omer Anis¹  Jacob Ramon¹  Stalin Nadarajan²  Eduard Belausov²  Dvora Namdar²  AjjampuraC Vinayaka²  Hinanit Koltai²  SeegehalliM Anil²  Nurit Shalev²  Ofer Cohen³  Einav Mayzlish Gati³ 

[1] Department of Urology, Sheba Medical Center, 52621 Ramat Gan, Israel;Institute of Plant Science, Agriculture Research Organization, Volcani Center, 7505101 Rishon LeZion, Israel;Israel Gene Bank, Agricultural Research Organization, Volcani Center, 7505101 Rishon LeZion, Israel;

关键词: apoptosis;    cannabis;    cannabinoids;    cancer;    F-actin;    urothelial carcinoma;   

DOI  :  10.3390/molecules26020465

来源: DOAJ

【 摘 要 】

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.

【 授权许可】

Unknown