Pro-Apoptotic Activity of <i>Epi</i>-Obtusane against Cervical Cancer: Nano Formulation, In Silico Molecular Docking, and Pharmacological Network Analysis
Cancer is a major disease that threatens human health all over the world. Intervention and prevention in premalignant processes are successful ways to prevent cancer from striking. On the other hand, the marine ecosystem is a treasure storehouse of promising bioactive metabolites. The use of such ma...
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| Format: | Article |
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MDPI AG
2023-11-01
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| Online Access: | https://www.mdpi.com/1424-8247/16/11/1578 |
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| author | Omnia Hesham Abdelhafez Islam M. Abdel-Rahman Eman Alaaeldin Hesham Refaat Refat El-Sayed Sami A. Al-Harbi Ahmed M. Shawky Mohamed-Elamir F. Hegazy Alaa Y. Moustafa Nourhan Hisham Shady |
| author_facet | Omnia Hesham Abdelhafez Islam M. Abdel-Rahman Eman Alaaeldin Hesham Refaat Refat El-Sayed Sami A. Al-Harbi Ahmed M. Shawky Mohamed-Elamir F. Hegazy Alaa Y. Moustafa Nourhan Hisham Shady |
| author_sort | Omnia Hesham Abdelhafez |
| collection | DOAJ |
| description | Cancer is a major disease that threatens human health all over the world. Intervention and prevention in premalignant processes are successful ways to prevent cancer from striking. On the other hand, the marine ecosystem is a treasure storehouse of promising bioactive metabolites. The use of such marine products can be optimized by selecting a suitable nanocarrier. Therefore, <i>epi</i>-obtusane, previously isolated from <i>Aplysia oculifera</i>, was investigated for its potential anticancer effects toward cervical cancer through a series of in vitro assays in HeLa cells using the MTT assay method. Additionally, the sesquiterpene was encapsulated within a liposomal formulation (size = 130.8 ± 50.3, PDI = 0.462, zeta potential −12.3 ± 2.3), and the antiproliferative potential of <i>epi</i>-obtusane was investigated against the human cervical cancer cell line HeLa before and after encapsulation with liposomes. <i>Epi</i>-obtusane exhibited a potent effect against the HeLa cell line, while the formulated molecule with liposomes increased the in vitro antiproliferative activity. Additionally, cell cycle arrest analysis, as well as the apoptosis assay, performed via FITC-Annexin-V/propidium iodide double staining (flow cytofluorimetry), were carried out. The pharmacological network enabled us to deliver further insights into the mechanism of <i>epi</i>-obtusane, suggesting that STAT3 might be targeted by the compound. Moreover, molecular docking showed a comparable binding score of the isolated compound towards the STAT3 SH2 domain. The targets possess an anticancer effect through the endometrial cancer pathway, regulation of DNA templated transcription, and nitric oxide synthase, as mentioned by the KEGG and ShinyGo 7.1 databases. |
| first_indexed | 2024-03-09T16:32:46Z |
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| id | doaj.art-dd7712a497a94bdaa8ac59484a812dba |
| institution | Directory Open Access Journal |
| issn | 1424-8247 |
| language | English |
| last_indexed | 2024-03-09T16:32:46Z |
| publishDate | 2023-11-01 |
| publisher | MDPI AG |
| record_format | Article |
| series | Pharmaceuticals |
| spelling | doaj.art-dd7712a497a94bdaa8ac59484a812dba2023-11-24T15:00:21ZengMDPI AGPharmaceuticals1424-82472023-11-011611157810.3390/ph16111578Pro-Apoptotic Activity of <i>Epi</i>-Obtusane against Cervical Cancer: Nano Formulation, In Silico Molecular Docking, and Pharmacological Network AnalysisOmnia Hesham Abdelhafez0Islam M. Abdel-Rahman1Eman Alaaeldin2Hesham Refaat3Refat El-Sayed4Sami A. Al-Harbi5Ahmed M. Shawky6Mohamed-Elamir F. Hegazy7Alaa Y. Moustafa8Nourhan Hisham Shady9Department of Pharmacognosy, Faculty of Pharmacy, Deraya University, Universities Zone, New Minia 61111, EgyptDepartment of Pharmaceutical Chemistry, Faculty of Pharmacy, Deraya University, New-Minia 61111, EgyptDepartment of Pharmaceutics, Faculty of Pharmacy, Minia University, Minia 61519, EgyptDepartment of Pharmaceutical Sciences and Experimental Therapeutics, College of Pharmacy, University of Iowa, Iowa City, IA 52246, USADepartment of Chemistry, University College in Al-Jamoum, Umm Al-Qura University, Makkah 24231, Saudi ArabiaDepartment of Chemistry, University College in Al-Jamoum, Umm Al-Qura University, Makkah 24231, Saudi ArabiaScience and Technology Unit (STU), Umm Al-Qura University, Makkah 21955, Saudi ArabiaChemistry of Medicinal Plants Department, National Research Centre, El-Tahrir Street, Dokki, Giza 12622, EgyptZoology Department, Faculty of Science, Sohag University, Sohag 82524, EgyptDepartment of Pharmacognosy, Faculty of Pharmacy, Deraya University, Universities Zone, New Minia 61111, EgyptCancer is a major disease that threatens human health all over the world. Intervention and prevention in premalignant processes are successful ways to prevent cancer from striking. On the other hand, the marine ecosystem is a treasure storehouse of promising bioactive metabolites. The use of such marine products can be optimized by selecting a suitable nanocarrier. Therefore, <i>epi</i>-obtusane, previously isolated from <i>Aplysia oculifera</i>, was investigated for its potential anticancer effects toward cervical cancer through a series of in vitro assays in HeLa cells using the MTT assay method. Additionally, the sesquiterpene was encapsulated within a liposomal formulation (size = 130.8 ± 50.3, PDI = 0.462, zeta potential −12.3 ± 2.3), and the antiproliferative potential of <i>epi</i>-obtusane was investigated against the human cervical cancer cell line HeLa before and after encapsulation with liposomes. <i>Epi</i>-obtusane exhibited a potent effect against the HeLa cell line, while the formulated molecule with liposomes increased the in vitro antiproliferative activity. Additionally, cell cycle arrest analysis, as well as the apoptosis assay, performed via FITC-Annexin-V/propidium iodide double staining (flow cytofluorimetry), were carried out. The pharmacological network enabled us to deliver further insights into the mechanism of <i>epi</i>-obtusane, suggesting that STAT3 might be targeted by the compound. Moreover, molecular docking showed a comparable binding score of the isolated compound towards the STAT3 SH2 domain. The targets possess an anticancer effect through the endometrial cancer pathway, regulation of DNA templated transcription, and nitric oxide synthase, as mentioned by the KEGG and ShinyGo 7.1 databases.https://www.mdpi.com/1424-8247/16/11/1578<i>aplysia</i><i>epi</i>-obtusanecervical cancerpharmacological networkliposomes |
| spellingShingle | Omnia Hesham Abdelhafez Islam M. Abdel-Rahman Eman Alaaeldin Hesham Refaat Refat El-Sayed Sami A. Al-Harbi Ahmed M. Shawky Mohamed-Elamir F. Hegazy Alaa Y. Moustafa Nourhan Hisham Shady Pro-Apoptotic Activity of <i>Epi</i>-Obtusane against Cervical Cancer: Nano Formulation, In Silico Molecular Docking, and Pharmacological Network Analysis Pharmaceuticals <i>aplysia</i> <i>epi</i>-obtusane cervical cancer pharmacological network liposomes |
| title | Pro-Apoptotic Activity of <i>Epi</i>-Obtusane against Cervical Cancer: Nano Formulation, In Silico Molecular Docking, and Pharmacological Network Analysis |
| title_full | Pro-Apoptotic Activity of <i>Epi</i>-Obtusane against Cervical Cancer: Nano Formulation, In Silico Molecular Docking, and Pharmacological Network Analysis |
| title_fullStr | Pro-Apoptotic Activity of <i>Epi</i>-Obtusane against Cervical Cancer: Nano Formulation, In Silico Molecular Docking, and Pharmacological Network Analysis |
| title_full_unstemmed | Pro-Apoptotic Activity of <i>Epi</i>-Obtusane against Cervical Cancer: Nano Formulation, In Silico Molecular Docking, and Pharmacological Network Analysis |
| title_short | Pro-Apoptotic Activity of <i>Epi</i>-Obtusane against Cervical Cancer: Nano Formulation, In Silico Molecular Docking, and Pharmacological Network Analysis |
| title_sort | pro apoptotic activity of i epi i obtusane against cervical cancer nano formulation in silico molecular docking and pharmacological network analysis |
| topic | <i>aplysia</i> <i>epi</i>-obtusane cervical cancer pharmacological network liposomes |
| url | https://www.mdpi.com/1424-8247/16/11/1578 |
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