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ORIGINAL ARTICLE
Year : 2022  |  Volume : 12  |  Issue : 8  |  Page : 323-332

Anticancer activity of Δ9-tetrahydrocannabinol and cannabinol in vitro and in human lung cancer xenograft


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

Correspondence Address:
Surang Leelawat
Medicinal Cannabis Research Institute, College of Pharmacy, Rangsit University, Pathum Thani 12000
Thailand
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Source of Support: This study was funded by a grant from the Research Institute, Rangsit University (grant number 103/2561, 2018) and by the College of Pharmacy, Rangsit University, Conflict of Interest: None


DOI: 10.4103/2221-1691.350180

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Objective: To investigate the effects of Δ9-tetrahydrocannabinol, the principal psychoactive compound of Cannabis sativa, and cannabinol, a Δ9-tetrahydrocannabinol degradative product, on human non-small cell lung cancer cells. Methods: Δ9-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 Δ9-tetrahydrocannabinol and cannabinol on tumor growth were also investigated using a xenograft nude mouse model. Apoptosis and targeted phosphorylation were verified by immunohistochemistry. Results: Δ9-Tetrahydrocannabinol and cannabinol significantly inhibited cell proliferation and increased the number of apoptotic cells in a concentration-dependent manner. The Δ9-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 Δ9-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 Δ9-tetrahydrocannabinol or 40 mg/kg cannabinol were significantly slower than in the control group. Conclusions: These findings indicate that Δ9-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.


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