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

Asian Pacific Journal of Tropical Biomedicine 2022年第8期12卷 323-332页

作者： 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 PharmacyRangsit UniversityPathum Thani 12000Thailand Department of Surgery Bumrungrad International HospitalBangkok 10110Thailand Drug and Herbal Product Research and Development Center College of PharmacyRangsit UniversityPathum Thani 12000Thailand College of Oriental Medicine Rangsit UniversityPathum Thani 12000Thailand Department of Pharmacognosy College of PharmacyRangsit UniversityPathum Thani 12000Thailand

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

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Role of cannabinoids and the endocannabinoid system in modulation of diabetic cardiomyopathy

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World Journal of Diabetes 2022年第5期13卷 387-407页

作者： Mona F El-Azab Ahmed E Wakiel Yossef K Nafea Mahmoud E Youssef Department of Pharmacology and Toxicology Faculty of PharmacySuez Canal UniversityIsmailia 41522Egypt Program of Biochemistry McMaster UniversityHamilton L8S 4L8OntarioCanada Department of Pharmacology and Biochemistry Delta University for Science and TechnologyMansoura 35511New CairoEgypt

Diabetic complications,chiefly seen in long-term situations,are persistently deleterious to a large extent,requiring multi-factorial risk reduction strategies beyond glycemic control.Diabetic cardiomyopathy is one of the most common deleterious diabetic complications,being the leading cause of mortality among diabetic patients.The mechanisms of diabetic cardiomyopathy are multi-factorial,involving increased oxidative stress,accumulation of advanced glycation end products(AGEs),activation of various pro-inflammatory and cell death signaling pathways,and changes in the composition of extracellular matrix with enhanced cardiac fibrosis.The novel lipid signaling system,the endocannabinoid system,has been implicated in the pathogenesis of diabetes and its complications through its two main receptors:Cannabinoid receptor type 1 and cannabinoid receptor type 2,alongside other components.However,the role of the endocannabinoid system in diabetic cardiomyopathy has not been fully investigated.This review aims to elucidate the possible mechanisms through which cannabinoids and the endocannabinoid system could interact with the pathogenesis and the development of diabetic cardiomyopathy.These mechanisms include oxidative/nitrative stress,inflammation,accumulation of AGEs,cardiac remodeling,and autophagy.A better understanding of the role of cannabinoids and the endocannabinoid system in diabetic cardiomyopathy may provide novel strategies to manipulate such a serious diabetic complication.

关键词： δ9-tetrahydrocannabinol Autophagy Cannabinoid receptors Diabetic cardiomyopathy Endocannabinoid system Inflammation

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