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Cannabis sativa demonstrates anti-hepatocellular carcinoma potentials in animal model: in silico and in vivo studies of the involvement of Akt
BACKGROUND: Targeting protein kinase B (Akt) and its downstream signaling proteins are promising options in designing novel and potent drug candidates against hepatocellular carcinoma (HCC). The present study explores the anti-HCC potentials of Cannabis sativa (C. sativa) extract via the involvement...
Autores principales: | , , , , , , |
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Formato: | Online Artículo Texto |
Lenguaje: | English |
Publicado: |
BioMed Central
2023
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Materias: | |
Acceso en línea: | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC10337064/ https://www.ncbi.nlm.nih.gov/pubmed/37434213 http://dx.doi.org/10.1186/s42238-023-00190-z |
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author | Akinloye, Dorcas I. Metibemu, Damilohun S. Shittu, Mujidat T. Lawal, Mariam A. Olatunji, Faith O. Oyediran, Muideen A. Akinloye, Oluseyi A. |
author_facet | Akinloye, Dorcas I. Metibemu, Damilohun S. Shittu, Mujidat T. Lawal, Mariam A. Olatunji, Faith O. Oyediran, Muideen A. Akinloye, Oluseyi A. |
author_sort | Akinloye, Dorcas I. |
collection | PubMed |
description | BACKGROUND: Targeting protein kinase B (Akt) and its downstream signaling proteins are promising options in designing novel and potent drug candidates against hepatocellular carcinoma (HCC). The present study explores the anti-HCC potentials of Cannabis sativa (C. sativa) extract via the involvement of Akt using both in silico and in vivo animal models of HCC approaches. METHODS: Phytoconstituents of C. sativa extract obtained from Gas Chromatography Mass-spectrometry (GCSM) were docked into the catalytic domain of Akt-2. The Diethylnitrosamine (DEN) model of HCC was treated with C. sativa extract. The effects of C. sativa extract treatments on DEN model of hepatocellular carcinoma were assessed by One-way analysis of variance (ANOVA) of the treated and untreated groups RESULT: The lead phytoconstituents of C. sativa extract, Δ-9-tetrahydrocannabinol (Δ-9-THC) and cannabidiol form stable hydrophobic and hydrogen bond interactions within the catalytic domain of Akt-2. C. sativa extract (15 mg/kg and 30 mg/kg) respectively gives a 3-fold decrease in the activities of liver function enzymes when compared with the positive control (group 2). It also gives a 1.5-fold decrease in hepatic lipid peroxidation and elevates serum antioxidant enzymes’ activities by 1-fold in HCC treated Wistar rats when compared with the positive control (group 2). In an animal model of hepatocellular carcinoma, C. sativa extract significantly downregulated Akt and HIF mRNAs in groups 3, 4, and 5 with 2, 1.5, 2.5-fold decrease relative to group 2. VEGF mRNA was downregulated by 1.5-fold decrease in groups 3-5 when compared to group 2. The expression of XIAP mRNA was downregulated by 1.5, 2, and 1.25-folds in groups 3, 4, and 5 respectively, in comparison with group 2. In comparison to group 2, COX-2 mRNA levels were downregulated by 1.5, 1, and 1-folds in groups 3–5. In groups 3–5, CRP mRNA was downregulated by 2-fold in comparison with group 2. In groups 3–5, p21 mRNA was upregulated by 2, 2.5, and 3-folds, respectively when compared with group 2. It upregulated p53 mRNA by 2.5, 3.5, and 2.5-folds in groups 3–5 in comparison with group 2. It downregulated AFP mRNA by 3.5, 2.5, .2.5-folds in groups 3, 4, and 5 respectively when compared with group 2. Histologic analysis showed that C. sativa extract reduced necrosis and inflammation in HCC. CONCLUSION: C. sativa demonstrates anti-hepatocellular carcinoma potentials in an animal model of HCC and with the involvement of Akt. Its anticancer potential is mediated through antiangiogenic, proapoptotic, cycle arrest, and anti-inflammatory mechanisms. In future studies, the mechanisms of anti-HCC effects of Δ-9-tetrahydrocannabinol (Δ-9- THC) and cannabidiol via the PI3K-Akt signaling pathways should be explored. |
format | Online Article Text |
id | pubmed-10337064 |
institution | National Center for Biotechnology Information |
language | English |
publishDate | 2023 |
publisher | BioMed Central |
record_format | MEDLINE/PubMed |
spelling | pubmed-103370642023-07-13 Cannabis sativa demonstrates anti-hepatocellular carcinoma potentials in animal model: in silico and in vivo studies of the involvement of Akt Akinloye, Dorcas I. Metibemu, Damilohun S. Shittu, Mujidat T. Lawal, Mariam A. Olatunji, Faith O. Oyediran, Muideen A. Akinloye, Oluseyi A. J Cannabis Res Original Research BACKGROUND: Targeting protein kinase B (Akt) and its downstream signaling proteins are promising options in designing novel and potent drug candidates against hepatocellular carcinoma (HCC). The present study explores the anti-HCC potentials of Cannabis sativa (C. sativa) extract via the involvement of Akt using both in silico and in vivo animal models of HCC approaches. METHODS: Phytoconstituents of C. sativa extract obtained from Gas Chromatography Mass-spectrometry (GCSM) were docked into the catalytic domain of Akt-2. The Diethylnitrosamine (DEN) model of HCC was treated with C. sativa extract. The effects of C. sativa extract treatments on DEN model of hepatocellular carcinoma were assessed by One-way analysis of variance (ANOVA) of the treated and untreated groups RESULT: The lead phytoconstituents of C. sativa extract, Δ-9-tetrahydrocannabinol (Δ-9-THC) and cannabidiol form stable hydrophobic and hydrogen bond interactions within the catalytic domain of Akt-2. C. sativa extract (15 mg/kg and 30 mg/kg) respectively gives a 3-fold decrease in the activities of liver function enzymes when compared with the positive control (group 2). It also gives a 1.5-fold decrease in hepatic lipid peroxidation and elevates serum antioxidant enzymes’ activities by 1-fold in HCC treated Wistar rats when compared with the positive control (group 2). In an animal model of hepatocellular carcinoma, C. sativa extract significantly downregulated Akt and HIF mRNAs in groups 3, 4, and 5 with 2, 1.5, 2.5-fold decrease relative to group 2. VEGF mRNA was downregulated by 1.5-fold decrease in groups 3-5 when compared to group 2. The expression of XIAP mRNA was downregulated by 1.5, 2, and 1.25-folds in groups 3, 4, and 5 respectively, in comparison with group 2. In comparison to group 2, COX-2 mRNA levels were downregulated by 1.5, 1, and 1-folds in groups 3–5. In groups 3–5, CRP mRNA was downregulated by 2-fold in comparison with group 2. In groups 3–5, p21 mRNA was upregulated by 2, 2.5, and 3-folds, respectively when compared with group 2. It upregulated p53 mRNA by 2.5, 3.5, and 2.5-folds in groups 3–5 in comparison with group 2. It downregulated AFP mRNA by 3.5, 2.5, .2.5-folds in groups 3, 4, and 5 respectively when compared with group 2. Histologic analysis showed that C. sativa extract reduced necrosis and inflammation in HCC. CONCLUSION: C. sativa demonstrates anti-hepatocellular carcinoma potentials in an animal model of HCC and with the involvement of Akt. Its anticancer potential is mediated through antiangiogenic, proapoptotic, cycle arrest, and anti-inflammatory mechanisms. In future studies, the mechanisms of anti-HCC effects of Δ-9-tetrahydrocannabinol (Δ-9- THC) and cannabidiol via the PI3K-Akt signaling pathways should be explored. BioMed Central 2023-07-12 /pmc/articles/PMC10337064/ /pubmed/37434213 http://dx.doi.org/10.1186/s42238-023-00190-z Text en © The Author(s) 2023 https://creativecommons.org/licenses/by/4.0/Open Access This article is licensed under a Creative Commons Attribution 4.0 International License, which permits use, sharing, adaptation, distribution and reproduction in any medium or format, as long as you give appropriate credit to the original author(s) and the source, provide a link to the Creative Commons licence, and indicate if changes were made. The images or other third party material in this article are included in the article's Creative Commons licence, unless indicated otherwise in a credit line to the material. If material is not included in the article's Creative Commons licence and your intended use is not permitted by statutory regulation or exceeds the permitted use, you will need to obtain permission directly from the copyright holder. To view a copy of this licence, visit http://creativecommons.org/licenses/by/4.0/ (https://creativecommons.org/licenses/by/4.0/) . |
spellingShingle | Original Research Akinloye, Dorcas I. Metibemu, Damilohun S. Shittu, Mujidat T. Lawal, Mariam A. Olatunji, Faith O. Oyediran, Muideen A. Akinloye, Oluseyi A. Cannabis sativa demonstrates anti-hepatocellular carcinoma potentials in animal model: in silico and in vivo studies of the involvement of Akt |
title | Cannabis sativa demonstrates anti-hepatocellular carcinoma potentials in animal model: in silico and in vivo studies of the involvement of Akt |
title_full | Cannabis sativa demonstrates anti-hepatocellular carcinoma potentials in animal model: in silico and in vivo studies of the involvement of Akt |
title_fullStr | Cannabis sativa demonstrates anti-hepatocellular carcinoma potentials in animal model: in silico and in vivo studies of the involvement of Akt |
title_full_unstemmed | Cannabis sativa demonstrates anti-hepatocellular carcinoma potentials in animal model: in silico and in vivo studies of the involvement of Akt |
title_short | Cannabis sativa demonstrates anti-hepatocellular carcinoma potentials in animal model: in silico and in vivo studies of the involvement of Akt |
title_sort | cannabis sativa demonstrates anti-hepatocellular carcinoma potentials in animal model: in silico and in vivo studies of the involvement of akt |
topic | Original Research |
url | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC10337064/ https://www.ncbi.nlm.nih.gov/pubmed/37434213 http://dx.doi.org/10.1186/s42238-023-00190-z |
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