Cannabis sativa demonstrates anti-hepatocellular carcinoma potentials in animal model: in silico and in vivo studies of the involvement of Akt
Abstract 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 inv...
| Main Authors: | , , , , , , |
|---|---|
| Format: | Article |
| Language: | English |
| Published: |
BMC
2023-07-01
|
| Series: | Journal of Cannabis Research |
| Subjects: | |
| Online Access: | https://doi.org/10.1186/s42238-023-00190-z |
| _version_ | 1797778693859311616 |
|---|---|
| author | Dorcas I. Akinloye Damilohun S. Metibemu Mujidat T. Shittu Mariam A. Lawal Faith O. Olatunji Muideen A. Oyediran Oluseyi A. Akinloye |
| author_facet | Dorcas I. Akinloye Damilohun S. Metibemu Mujidat T. Shittu Mariam A. Lawal Faith O. Olatunji Muideen A. Oyediran Oluseyi A. Akinloye |
| author_sort | Dorcas I. Akinloye |
| collection | DOAJ |
| description | Abstract 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. |
| first_indexed | 2024-03-12T23:21:08Z |
| format | Article |
| id | doaj.art-4b5164c057c2442cb28331805dc565bb |
| institution | Directory Open Access Journal |
| issn | 2522-5782 |
| language | English |
| last_indexed | 2024-03-12T23:21:08Z |
| publishDate | 2023-07-01 |
| publisher | BMC |
| record_format | Article |
| series | Journal of Cannabis Research |
| spelling | doaj.art-4b5164c057c2442cb28331805dc565bb2023-07-16T11:26:53ZengBMCJournal of Cannabis Research2522-57822023-07-015111310.1186/s42238-023-00190-zCannabis sativa demonstrates anti-hepatocellular carcinoma potentials in animal model: in silico and in vivo studies of the involvement of AktDorcas I. Akinloye0Damilohun S. Metibemu1Mujidat T. Shittu2Mariam A. Lawal3Faith O. Olatunji4Muideen A. Oyediran5Oluseyi A. Akinloye6Department of Biochemistry, Phyto-chemistry and Bio-computing Research Laboratory, College of Biosciences, Federal University of AgricultureDepartment of Chemistry, Physics, and Atmospheric Sciences, Jackson State UniversityDepartment of Biochemistry, Phyto-chemistry and Bio-computing Research Laboratory, College of Biosciences, Federal University of AgricultureDepartment of Biochemistry, Phyto-chemistry and Bio-computing Research Laboratory, College of Biosciences, Federal University of AgricultureDepartment of Biochemistry, Phyto-chemistry and Bio-computing Research Laboratory, College of Biosciences, Federal University of AgricultureDepartment of Biochemistry, Phyto-chemistry and Bio-computing Research Laboratory, College of Biosciences, Federal University of AgricultureDepartment of Biochemistry, Phyto-chemistry and Bio-computing Research Laboratory, College of Biosciences, Federal University of AgricultureAbstract 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.https://doi.org/10.1186/s42238-023-00190-zAnti-angiogenicProapoptoticAnti-inflammatoryΔ-9-tetrahydrocannabinolCannabidiol |
| spellingShingle | Dorcas I. Akinloye Damilohun S. Metibemu Mujidat T. Shittu Mariam A. Lawal Faith O. Olatunji Muideen A. Oyediran Oluseyi A. Akinloye Cannabis sativa demonstrates anti-hepatocellular carcinoma potentials in animal model: in silico and in vivo studies of the involvement of Akt Journal of Cannabis Research Anti-angiogenic Proapoptotic Anti-inflammatory Δ-9-tetrahydrocannabinol Cannabidiol |
| 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 | Anti-angiogenic Proapoptotic Anti-inflammatory Δ-9-tetrahydrocannabinol Cannabidiol |
| url | https://doi.org/10.1186/s42238-023-00190-z |
| work_keys_str_mv | AT dorcasiakinloye cannabissativademonstratesantihepatocellularcarcinomapotentialsinanimalmodelinsilicoandinvivostudiesoftheinvolvementofakt AT damilohunsmetibemu cannabissativademonstratesantihepatocellularcarcinomapotentialsinanimalmodelinsilicoandinvivostudiesoftheinvolvementofakt AT mujidattshittu cannabissativademonstratesantihepatocellularcarcinomapotentialsinanimalmodelinsilicoandinvivostudiesoftheinvolvementofakt AT mariamalawal cannabissativademonstratesantihepatocellularcarcinomapotentialsinanimalmodelinsilicoandinvivostudiesoftheinvolvementofakt AT faithoolatunji cannabissativademonstratesantihepatocellularcarcinomapotentialsinanimalmodelinsilicoandinvivostudiesoftheinvolvementofakt AT muideenaoyediran cannabissativademonstratesantihepatocellularcarcinomapotentialsinanimalmodelinsilicoandinvivostudiesoftheinvolvementofakt AT oluseyiaakinloye cannabissativademonstratesantihepatocellularcarcinomapotentialsinanimalmodelinsilicoandinvivostudiesoftheinvolvementofakt |