Anticancer activity of Δ^(9)-tetrahydrocannabinol and cannabinol in vitro and in human lung cancer xenograft  

作　　者：Surang Leelawat Kawin Leelawat Thaniya Wannakup Worawan Saingam Nanthaphong Khamthong Fameera Madaka Athip Maha Patamaporn Pathompak Lukman Sueree Thanapat Songsak 

机构地区：[1]Medicinal Cannabis Research Institute,College of Pharmacy,Rangsit University,Pathum Thani 12000,Thailand [2]Department of Surgery,Bumrungrad International Hospital,Bangkok 10110,Thailand [3]Drug and Herbal Product Research and Development Center,College of Pharmacy,Rangsit University,Pathum Thani 12000,Thailand [4]College of Oriental Medicine,Rangsit University,Pathum Thani 12000,Thailand [5]Department of Pharmacognosy,College of Pharmacy,Rangsit University,Pathum Thani 12000,Thailand

出　　处：《Asian Pacific Journal of Tropical Biomedicine》2022年第8期323-332,共10页亚太热带生物医学杂志（英文版）

基　　金：the Research Institute,Rangsit University(grant number 103/2561,2018)and by the College of Pharmacy,Rangsit University.

摘　　要：Objective:To investigate the effects of Δ^(9)-tetrahydrocannabinol,the principal psychoactive compound of Cannabis sativa,and cannabinol,a Δ^(9)-tetrahydrocannabinol degradative product,on human non-small cell lung cancer cells.Methods:Δ^(9)-Tetrahydrocannabinol and cannabinol were tested for anticancer activity in human non-small cell lung cancer(A549)cells.The effects on cell proliferation,apoptosis,and phosphorylation profiles were examined.The effects of Δ^(9)-tetrahydrocannabinol and cannabinol on tumor growth were also investigated using a xenograft nude mouse model.Apoptosis and targeted phosphorylation were verified by immunohistochemistry.Results:Δ^(9)-Tetrahydrocannabinol and cannabinol significantly inhibited cell proliferation and increased the number of apoptotic cells in a concentration-dependent manner.The Δ^(9)-tetrahydrocannabinol-and cannabinol-treated cells had lower levels of phosphorylated protein kinase B[AKT(S473)],glycogen synthase kinase 3 alpha/beta,and endothelial nitric oxide synthase compared to the controls.The study of xenograft mice revealed that tumors treated with 15 mg/kg Δ^(9)-tetrahydrocannabinol or 40 mg/kg cannabinol were significantly smaller than those of the control mice.The tumor progression rates in mice treated with 15 mg/kg Δ^(9)-tetrahydrocannabinol or 40 mg/kg cannabinol were significantly slower than in the control group.Conclusions:These findings indicate that Δ^(9)-tetrahydrocannabinol and cannabinol inhibit lung cancer cell growth by inhibiting AKT and its signaling pathways,which include glycogen synthase kinase 3 alpha/beta and endothelial nitric oxide synthase.

关 键 词：CANNABIS Δ9-Tetrahydrocannabinol Cannabinol Non-small cell lung cancer AKT Cannabis sativa Glycogen synthase kinase 3 alpha/beta Endothelial nitric oxide synthase 

分 类 号：R285[医药卫生—中药学]