Asian Pacific Journal of Tropical Biomedicine

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


Surang Leelawat1, Kawin Leelawat2, Thaniya Wannakup3, Worawan Saingam3, Nanthaphong Khamthong4, Fameera Madaka3, Athip Maha3, Patamaporn Pathompak3, Lukman Sueree3, Thanapat Songsak5 
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

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.


How to cite this article:
Leelawat S, Leelawat K, Wannakup T, Saingam W, Khamthong N, Madaka F, Maha A, Pathompak P, Sueree L, Songsak T. Anticancer activity of Δ9-tetrahydrocannabinol and cannabinol in vitro and in human lung cancer xenograft.Asian Pac J Trop Biomed 2022;12:323-332


How to cite this URL:
Leelawat S, Leelawat K, Wannakup T, Saingam W, Khamthong N, Madaka F, Maha A, Pathompak P, Sueree L, Songsak T. Anticancer activity of Δ9-tetrahydrocannabinol and cannabinol in vitro and in human lung cancer xenograft. Asian Pac J Trop Biomed [serial online] 2022 [cited 2022 Aug 18 ];12:323-332
Available from: https://www.apjtb.org/article.asp?issn=2221-1691;year=2022;volume=12;issue=8;spage=323;epage=332;aulast=Leelawat;type=0