Objective: To investigate the effects of ?9-tetrahydrocannabinol, the principal psychoactive compound of Cannabis sativa, and cannabinol, a ?9-tetrahydrocannabinol degradative product, on human non-small cell lung cancer cells.Methods: ?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 ?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: ?9-Tetrahydrocannabinol and cannabinol significantly inhibited cell proliferation and increased the number of apoptotic cells in a concentration-dependent manner. The ?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 ?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 ?9-tetrahydrocannabinol or 40 mg/kg cannabinol were significantly slower than in the control group. Conclusions: These findings indicate that ?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.

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

Medicinal Cannabis Research Institute,College of Pharmacy,Rangsit University,Pathum Thani 12000,Thailand;Department of Surgery,Bumrungrad International Hospital,Bangkok 10110,Thailand;Drug and Herbal Product Research and Development Center,College of Pharmacy,Rangsit University,Pathum Thani 12000,Thailand;College of Oriental Medicine,Rangsit University,Pathum Thani 12000,Thailand;Department of Pharmacognosy,College of Pharmacy,Rangsit University,Pathum Thani 12000,Thailand

亚太热带生物医学杂志（英文版）

[1]Surang Leelawat;Kawin Leelawat;Thaniya Wannakup;Worawan Saingam;Nanthaphong Khamthong;Fameera Madaka;Athip Maha;Patamaporn Pathompak;Lukman Sueree;Thanapat Songsak-.Anticancer activity of ?9-tetrahydrocannabinol and cannabinol in vitro and in human lung cancer xenograft)[J].亚太热带生物医学杂志（英文版）,2022(08):323-332

cannabinol,Tetrahydrocannabinol

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