Anticancer activity of Δ9-tetrahydrocannabinol and cannabinol in vitro and in human lung cancer xenograft
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 anticanc...
Published in: | Asian Pacific Journal of Tropical Biomedicine |
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Wolters Kluwer Medknow Publications
2022
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Online Access: | https://doi.org/10.4103/2221-1691.350180 https://doaj.org/article/056395876eb84491973b535e5a352a37 |
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ftdoajarticles:oai:doaj.org/article:056395876eb84491973b535e5a352a37 2023-05-15T15:11:24+02:00 Anticancer activity of Δ9-tetrahydrocannabinol and cannabinol in vitro and in human lung cancer xenograft Surang Leelawat Kawin Leelawat Thaniya Wannakup Worawan Saingam Nanthaphong Khamthong Fameera Madaka Athip Maha Patamaporn Pathompak Lukman Sueree Thanapat Songsak 2022-01-01T00:00:00Z https://doi.org/10.4103/2221-1691.350180 https://doaj.org/article/056395876eb84491973b535e5a352a37 EN eng Wolters Kluwer Medknow Publications http://www.apjtb.org/article.asp?issn=2221-1691;year=2022;volume=12;issue=8;spage=323;epage=332;aulast=Leelawat https://doaj.org/toc/2221-1691 https://doaj.org/toc/2588-9222 2221-1691 2588-9222 doi:10.4103/2221-1691.350180 https://doaj.org/article/056395876eb84491973b535e5a352a37 Asian Pacific Journal of Tropical Biomedicine, Vol 12, Iss 8, Pp 323-332 (2022) cannabis δ9-tetrahydrocannabinol cannabinol non-small cell lung cancer akt cannabis sativa glycogen synthase kinase 3 alpha/beta endothelial nitric oxide synthase Arctic medicine. Tropical medicine RC955-962 Biology (General) QH301-705.5 article 2022 ftdoajarticles https://doi.org/10.4103/2221-1691.350180 2022-12-30T22:08:54Z 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. Article in Journal/Newspaper Arctic Directory of Open Access Journals: DOAJ Articles Arctic Asian Pacific Journal of Tropical Biomedicine 12 8 323 |
institution |
Open Polar |
collection |
Directory of Open Access Journals: DOAJ Articles |
op_collection_id |
ftdoajarticles |
language |
English |
topic |
cannabis δ9-tetrahydrocannabinol cannabinol non-small cell lung cancer akt cannabis sativa glycogen synthase kinase 3 alpha/beta endothelial nitric oxide synthase Arctic medicine. Tropical medicine RC955-962 Biology (General) QH301-705.5 |
spellingShingle |
cannabis δ9-tetrahydrocannabinol cannabinol non-small cell lung cancer akt cannabis sativa glycogen synthase kinase 3 alpha/beta endothelial nitric oxide synthase Arctic medicine. Tropical medicine RC955-962 Biology (General) QH301-705.5 Surang Leelawat Kawin Leelawat Thaniya Wannakup Worawan Saingam Nanthaphong Khamthong Fameera Madaka Athip Maha Patamaporn Pathompak Lukman Sueree Thanapat Songsak Anticancer activity of Δ9-tetrahydrocannabinol and cannabinol in vitro and in human lung cancer xenograft |
topic_facet |
cannabis δ9-tetrahydrocannabinol cannabinol non-small cell lung cancer akt cannabis sativa glycogen synthase kinase 3 alpha/beta endothelial nitric oxide synthase Arctic medicine. Tropical medicine RC955-962 Biology (General) QH301-705.5 |
description |
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. |
format |
Article in Journal/Newspaper |
author |
Surang Leelawat Kawin Leelawat Thaniya Wannakup Worawan Saingam Nanthaphong Khamthong Fameera Madaka Athip Maha Patamaporn Pathompak Lukman Sueree Thanapat Songsak |
author_facet |
Surang Leelawat Kawin Leelawat Thaniya Wannakup Worawan Saingam Nanthaphong Khamthong Fameera Madaka Athip Maha Patamaporn Pathompak Lukman Sueree Thanapat Songsak |
author_sort |
Surang Leelawat |
title |
Anticancer activity of Δ9-tetrahydrocannabinol and cannabinol in vitro and in human lung cancer xenograft |
title_short |
Anticancer activity of Δ9-tetrahydrocannabinol and cannabinol in vitro and in human lung cancer xenograft |
title_full |
Anticancer activity of Δ9-tetrahydrocannabinol and cannabinol in vitro and in human lung cancer xenograft |
title_fullStr |
Anticancer activity of Δ9-tetrahydrocannabinol and cannabinol in vitro and in human lung cancer xenograft |
title_full_unstemmed |
Anticancer activity of Δ9-tetrahydrocannabinol and cannabinol in vitro and in human lung cancer xenograft |
title_sort |
anticancer activity of δ9-tetrahydrocannabinol and cannabinol in vitro and in human lung cancer xenograft |
publisher |
Wolters Kluwer Medknow Publications |
publishDate |
2022 |
url |
https://doi.org/10.4103/2221-1691.350180 https://doaj.org/article/056395876eb84491973b535e5a352a37 |
geographic |
Arctic |
geographic_facet |
Arctic |
genre |
Arctic |
genre_facet |
Arctic |
op_source |
Asian Pacific Journal of Tropical Biomedicine, Vol 12, Iss 8, Pp 323-332 (2022) |
op_relation |
http://www.apjtb.org/article.asp?issn=2221-1691;year=2022;volume=12;issue=8;spage=323;epage=332;aulast=Leelawat https://doaj.org/toc/2221-1691 https://doaj.org/toc/2588-9222 2221-1691 2588-9222 doi:10.4103/2221-1691.350180 https://doaj.org/article/056395876eb84491973b535e5a352a37 |
op_doi |
https://doi.org/10.4103/2221-1691.350180 |
container_title |
Asian Pacific Journal of Tropical Biomedicine |
container_volume |
12 |
container_issue |
8 |
container_start_page |
323 |
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1766342256746299392 |