Optimized bilosome-based nanoparticles enhance cytotoxic and pro-apoptotic activity of costunolide in LS174T colon cancer cells
Costunolide (COST) is a sesquiterpene lactone that belongs to the germacranolide group, and occurs mainly in Saussurea lappa Clarke. Although COST inhibits the proliferation and metastasis of cancer cells and induces their apoptosis, it suffers poor water solubility and cellular permeability. Theref...
| Main Authors: | , , , , , , , , , , |
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| Format: | Article |
| Language: | English |
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Elsevier
2023-12-01
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| Series: | Biomedicine & Pharmacotherapy |
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| Online Access: | http://www.sciencedirect.com/science/article/pii/S075333222301555X |
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| author | Abdulmohsin J. Alamoudi Shaimaa M. Badr-Eldin Osama A.A. Ahmed Usama A. Fahmy Serag Eldin I. Elbehairi Mohammad Y. Alfaifi Hani Z. Asfour Gamal A. Mohamed Sabrin R.M. Ibrahim Ashraf B. Abdel-Naim Hossam M. Abdallah |
| author_facet | Abdulmohsin J. Alamoudi Shaimaa M. Badr-Eldin Osama A.A. Ahmed Usama A. Fahmy Serag Eldin I. Elbehairi Mohammad Y. Alfaifi Hani Z. Asfour Gamal A. Mohamed Sabrin R.M. Ibrahim Ashraf B. Abdel-Naim Hossam M. Abdallah |
| author_sort | Abdulmohsin J. Alamoudi |
| collection | DOAJ |
| description | Costunolide (COST) is a sesquiterpene lactone that belongs to the germacranolide group, and occurs mainly in Saussurea lappa Clarke. Although COST inhibits the proliferation and metastasis of cancer cells and induces their apoptosis, it suffers poor water solubility and cellular permeability. Therefore, this study aimed to enhance the anti-proliferative activity of COST in LS174T colon cancer cells through its inclusion in bilosomal nanoformulation (COST-BILs). The optimized BIL formula contained cholesterol and Span-85 in a molar ratio of 1:5 as well as bile salt at a molar concentration of 0.5 mM, with entrapment efficiency of 63.4 ± 3.59 % and particle size of 119.7 ± 3.63 nm. The optimized COST-BILs showed a potent cytotoxic effect against LS174T cells with an IC50 of 6.20 µM; meanwhile, raw COST had an IC50 of 15.78 µM. Safety and relative selectivity were confirmed in the normal human colonic epithelial cells (HCoEpC). Cell cycle analysis indicated that both raw COST and COST-BILs significantly increased the fraction of LS174T cells in the sub-G1 phase. This was accompanied by a significant enhancement of early, late, and total apoptosis, as indicated by annexin-V staining. In addition, COST-BILs exhibited more potent activity in up-regulating CASP3, TP53, and BAX, and in down-regulating the expression of BCL2 mRNA as compared to raw COST. Further, the prepared formula enhanced the release of cytochrome C as well as the generation of reactive oxygen species (ROS) and reduced the integrity of mitochondrial membranes. In conclusion, the loading of COST on BILs significantly enhances its pro-apoptotic activity in LS174T cells. |
| first_indexed | 2024-03-11T11:10:41Z |
| format | Article |
| id | doaj.art-8a480ef25a6f414b89040563299e5000 |
| institution | Directory Open Access Journal |
| issn | 0753-3322 |
| language | English |
| last_indexed | 2024-03-11T11:10:41Z |
| publishDate | 2023-12-01 |
| publisher | Elsevier |
| record_format | Article |
| series | Biomedicine & Pharmacotherapy |
| spelling | doaj.art-8a480ef25a6f414b89040563299e50002023-11-12T04:39:12ZengElsevierBiomedicine & Pharmacotherapy0753-33222023-12-01168115757Optimized bilosome-based nanoparticles enhance cytotoxic and pro-apoptotic activity of costunolide in LS174T colon cancer cellsAbdulmohsin J. Alamoudi0Shaimaa M. Badr-Eldin1Osama A.A. Ahmed2Usama A. Fahmy3Serag Eldin I. Elbehairi4Mohammad Y. Alfaifi5Hani Z. Asfour6Gamal A. Mohamed7Sabrin R.M. Ibrahim8Ashraf B. Abdel-Naim9Hossam M. Abdallah10Department of Pharmacology and Toxicology, Faculty of Pharmacy, King Abdulaziz University, Jeddah 21589, Saudi ArabiaDepartment of Pharmaceutics, Faculty of Pharmacy, King Abdulaziz University, Jeddah 21589, Saudi ArabiaDepartment of Pharmaceutics, Faculty of Pharmacy, King Abdulaziz University, Jeddah 21589, Saudi ArabiaDepartment of Pharmaceutics, Faculty of Pharmacy, King Abdulaziz University, Jeddah 21589, Saudi ArabiaBiology Department, Faculty of Science, King Khalid University, Abha, Saudi Arabia; Cell Culture Lab, Egyptian Organization for Biological Products and Vaccines (VACSERA Holding Company), 51 Wezaret El-Zeraa St., Agouza, Giza, EgyptBiology Department, Faculty of Science, King Khalid University, Abha, Saudi ArabiaDepartment of Clinical Microbiology and Immunology, Faculty of Medicine, King Abdulaziz University, Jeddah 21589, Saudi ArabiaDepartment of Natural Products and Alternative Medicine, Faculty of Pharmacy, King Abdulaziz University, Jeddah 21589, Saudi ArabiaDepartment of Chemistry, Preparatory Year Program, Batterjee Medical College, Jeddah 21442, Saudi Arabia; Department of Pharmacognosy, Faculty of Pharmacy, Assiut University, Assiut 71526, EgyptDepartment of Pharmacology and Toxicology, Faculty of Pharmacy, King Abdulaziz University, Jeddah 21589, Saudi ArabiaDepartment of Natural Products and Alternative Medicine, Faculty of Pharmacy, King Abdulaziz University, Jeddah 21589, Saudi Arabia; Corresponding author.Costunolide (COST) is a sesquiterpene lactone that belongs to the germacranolide group, and occurs mainly in Saussurea lappa Clarke. Although COST inhibits the proliferation and metastasis of cancer cells and induces their apoptosis, it suffers poor water solubility and cellular permeability. Therefore, this study aimed to enhance the anti-proliferative activity of COST in LS174T colon cancer cells through its inclusion in bilosomal nanoformulation (COST-BILs). The optimized BIL formula contained cholesterol and Span-85 in a molar ratio of 1:5 as well as bile salt at a molar concentration of 0.5 mM, with entrapment efficiency of 63.4 ± 3.59 % and particle size of 119.7 ± 3.63 nm. The optimized COST-BILs showed a potent cytotoxic effect against LS174T cells with an IC50 of 6.20 µM; meanwhile, raw COST had an IC50 of 15.78 µM. Safety and relative selectivity were confirmed in the normal human colonic epithelial cells (HCoEpC). Cell cycle analysis indicated that both raw COST and COST-BILs significantly increased the fraction of LS174T cells in the sub-G1 phase. This was accompanied by a significant enhancement of early, late, and total apoptosis, as indicated by annexin-V staining. In addition, COST-BILs exhibited more potent activity in up-regulating CASP3, TP53, and BAX, and in down-regulating the expression of BCL2 mRNA as compared to raw COST. Further, the prepared formula enhanced the release of cytochrome C as well as the generation of reactive oxygen species (ROS) and reduced the integrity of mitochondrial membranes. In conclusion, the loading of COST on BILs significantly enhances its pro-apoptotic activity in LS174T cells.http://www.sciencedirect.com/science/article/pii/S075333222301555XCostunolideBilosomesApoptosisAnti-proliferative activityColon cancerDrug discovery |
| spellingShingle | Abdulmohsin J. Alamoudi Shaimaa M. Badr-Eldin Osama A.A. Ahmed Usama A. Fahmy Serag Eldin I. Elbehairi Mohammad Y. Alfaifi Hani Z. Asfour Gamal A. Mohamed Sabrin R.M. Ibrahim Ashraf B. Abdel-Naim Hossam M. Abdallah Optimized bilosome-based nanoparticles enhance cytotoxic and pro-apoptotic activity of costunolide in LS174T colon cancer cells Biomedicine & Pharmacotherapy Costunolide Bilosomes Apoptosis Anti-proliferative activity Colon cancer Drug discovery |
| title | Optimized bilosome-based nanoparticles enhance cytotoxic and pro-apoptotic activity of costunolide in LS174T colon cancer cells |
| title_full | Optimized bilosome-based nanoparticles enhance cytotoxic and pro-apoptotic activity of costunolide in LS174T colon cancer cells |
| title_fullStr | Optimized bilosome-based nanoparticles enhance cytotoxic and pro-apoptotic activity of costunolide in LS174T colon cancer cells |
| title_full_unstemmed | Optimized bilosome-based nanoparticles enhance cytotoxic and pro-apoptotic activity of costunolide in LS174T colon cancer cells |
| title_short | Optimized bilosome-based nanoparticles enhance cytotoxic and pro-apoptotic activity of costunolide in LS174T colon cancer cells |
| title_sort | optimized bilosome based nanoparticles enhance cytotoxic and pro apoptotic activity of costunolide in ls174t colon cancer cells |
| topic | Costunolide Bilosomes Apoptosis Anti-proliferative activity Colon cancer Drug discovery |
| url | http://www.sciencedirect.com/science/article/pii/S075333222301555X |
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