“Cannabis sativa is an agriculturally and medicinally important plant with many pharmaceutical properties. Cancer is a deadly disease; it is estimated that it will cause over 80 thousand deaths in 2019 in Canada. Although numerous studies have demonstrated that cannabinoids have anti-tumorous properties in various cancers, the anti-malignant activities of cannabinol (CBN) on carcinogenesis and underlying mechanisms remain largely unknown. In this study, we provide evidence that CBN inhibits proliferation of A172, HB8065 and HCC1806 cells in a dose- and time-dependent manner. CBN regulates expression of cannabinoid receptors, CB2, GPR55 and GPR18 in different cell lines, while reducing levels of phosphorylated ERK1/2 in HCC1806 and phosphorylated AKT in A172 and HB8065 cells. We find that CBN induces apoptosis through downregulation of p21 and p27 and a G1 or S-phase cell cycle arrest through a dose-dependent downregulation of cyclin E1, CDK1 and CDK2. These data support the medicinal potential of CBN in anti-cancer therapy.”
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