Novel 3′-diindolylmethane nanoformulation induces apoptosis, and reduces migration and angiogenesis in liver cancer cells
Liver cancer (LC) ranks as the second most prevalent cause of cancer-related deaths. Herbaceous plants are valuable sources of complementary, adjuvant, or alternative anti-tumor therapy as they contain natural active ingredients with anti-cancer potential. Although the clinical use of 3, 3′-Diindoly...
| Main Authors: | , , , , , , , , , , , , , |
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| Format: | Article |
| Language: | English |
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Elsevier
2023-11-01
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| Series: | Journal of King Saud University: Science |
| Subjects: | |
| Online Access: | http://www.sciencedirect.com/science/article/pii/S1018364723003269 |
| _version_ | 1797653937942167552 |
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| author | Steve Harakeh Saber H. Saber Turki alamri Rajaa Al-Raddadi Soad Al-Jaouni Hanaa Tashkandi Mohammed Qari Yousef Qari Isaac O. Akefe Zakariya Y. Abd Elmageed Shafiul Haque Anwar M Hashem Eram Albajri Shaker Mousa |
| author_facet | Steve Harakeh Saber H. Saber Turki alamri Rajaa Al-Raddadi Soad Al-Jaouni Hanaa Tashkandi Mohammed Qari Yousef Qari Isaac O. Akefe Zakariya Y. Abd Elmageed Shafiul Haque Anwar M Hashem Eram Albajri Shaker Mousa |
| author_sort | Steve Harakeh |
| collection | DOAJ |
| description | Liver cancer (LC) ranks as the second most prevalent cause of cancer-related deaths. Herbaceous plants are valuable sources of complementary, adjuvant, or alternative anti-tumor therapy as they contain natural active ingredients with anti-cancer potential. Although the clinical use of 3, 3′-Diindolylmethane (DIM) has been established, its low chemical stability and bioavailability, limits its therapeutic applications. Increasing effort has been undertaken to improve DIM’s biological activity including nanoformulations. Here, we evaluated the efficacy of DIM nanoparticles (DIM-NPs) coated with PEG/chitosan for the treatment of liver cancer and elucidated the underlying molecular mechanisms contributing to its anti-tumor activity. DIM-PLGA-PEG/chitosan NPs were synthesized and characterized using dynamic light scattering (DLS). The effect of newly synthesized DIM-NPs was evaluated in HepG-2 and HUH-7 hepatocarcinoma cells and compared to THLE-2 immortal normal liver cells and WI-38 (normal lung fibroblast cells). These cells were treated with different non-cytotoxic concentrations of DIM-NPs and MTT assay and other functional assays were performed. Compared to normal cells, DIM-NPs induced cytotoxicity in HepG-2 cells at 6.25 µg/mL after 48 h of treatment. Treatment of HepG-2 cells with the 50 % inhibitory concentration (IC50) 12.5 µg/mL of DIM-NPs inhibited cell migration (p < 0.001). Treatment of chicken embryo with 5ug/ml DIM-NPs reduced (p < 0.001) angiogenesis at day 4. Notably, at the molecular level, DIM-NPs upregulated Bax and p53 and downregulated Bcl-2 in a dose-dependent manner. DIM-NPs also induced cell apoptosis in HepG-2 cells. Treatment of hepatic cells with DIM-NPs decreased cell proliferation, migration and angiogenesis, and induced cell death via up-regulation of Bax and p53, and down-regulation of Bcl-2 in HepG-2 cells. Further investigations are necessitated to determine the pharmacokinetics of DIM-NPs using a preclinical cancer model. |
| first_indexed | 2024-03-11T16:52:06Z |
| format | Article |
| id | doaj.art-1dc8c31c920d43d1ba5d14a677343473 |
| institution | Directory Open Access Journal |
| issn | 1018-3647 |
| language | English |
| last_indexed | 2024-03-11T16:52:06Z |
| publishDate | 2023-11-01 |
| publisher | Elsevier |
| record_format | Article |
| series | Journal of King Saud University: Science |
| spelling | doaj.art-1dc8c31c920d43d1ba5d14a6773434732023-10-21T04:22:08ZengElsevierJournal of King Saud University: Science1018-36472023-11-01358102864Novel 3′-diindolylmethane nanoformulation induces apoptosis, and reduces migration and angiogenesis in liver cancer cellsSteve Harakeh0Saber H. Saber1Turki alamri2Rajaa Al-Raddadi3Soad Al-Jaouni4Hanaa Tashkandi5Mohammed Qari6Yousef Qari7Isaac O. Akefe8Zakariya Y. Abd Elmageed9Shafiul Haque10Anwar M Hashem11Eram Albajri12Shaker Mousa13King Fahd Medical Research Center, King Abdulaziz University, Jeddah, Saudi Arabia; Yousef Abdul Latif Jameel Scientific Chair of Prophetic Medicine Application, Faculty of Medicine, King Abdulaziz University, Jeddah, Saudi Arabia; Corresponding authors at: King Fahd Medical Research Center, King Abdulaziz University, Jeddah, Saudi Arabia (S. Harakeh).Laboratory of Molecular Cell Biology, Department of Zoology, Faculty of Science, Assiut University, Assiut 71515, EgyptFamily and Community Medicine Department, Faculty of Medicine in Rabigh, King Abdulaziz University, Jeddah, Saudi ArabiaDepartment of Community Medicine, Faculty of Medicine, King Abdulaziz University, Saudi ArabiaYousef Abdul Latif Jameel Scientific Chair of Prophetic Medicine Application, Faculty of Medicine, King Abdulaziz University, Jeddah, Saudi Arabia; Department of Hematology/ Pediatric Oncology, King Abdulaziz University Hospital, FM, King Abdulaziz University, Jeddah, Saudi ArabiaDepartment of Surgery, Faculty of Medicine, King Abdulaziz University, Jeddah, Saudi ArabiaYousef Abdul Latif Jameel Scientific Chair of Prophetic Medicine Application, Faculty of Medicine, King Abdulaziz University, Jeddah, Saudi Arabia; Department of Hematology/ Pediatric Oncology, King Abdulaziz University Hospital, FM, King Abdulaziz University, Jeddah, Saudi ArabiaDepartment of Medicine, King Abdulaziz University Hospital, King Abdulaziz University, Jeddah, Saudi ArabiaDepartment of Physiology, Biochemistry and Pharmacology, Faculty of Veterinary Medicine, University of Jos, NigeriaDepartment of Pharmacology, Edward Via College of Osteopathic Medicine, University of Louisiana at Monroe, Monroe, LA 71203, USAResearch and Scientific Studies Unit, College of Nursing and Allied Health Sciences, Jazan University, Jazan 45142, Saudi Arabia; Bursa Uludağ University Faculty of Medicine, Görükle Campus, 16059 Nilüfer, Bursa, TurkeyDepartment of Medical Microbiology and Parasitology, Faculty of Medicine, King Abdulaziz University, Jeddah 21589, Saudi Arabia; Vaccine and Immunotherapy Unit, King Fahd Medical Research Center, Jeddah 21589, Saudi ArabiaClinical Nutrition Department, Faculty of Applied Medical Sciences, King Abdulaziz University, Jeddah 21589, Saudi ArabiaPharmaceutical Research Institute, Albany College of Pharmacy and Health Sciences, Rensselaer, NY 12144, USA; Corresponding authors at: King Fahd Medical Research Center, King Abdulaziz University, Jeddah, Saudi Arabia (S. Harakeh).Liver cancer (LC) ranks as the second most prevalent cause of cancer-related deaths. Herbaceous plants are valuable sources of complementary, adjuvant, or alternative anti-tumor therapy as they contain natural active ingredients with anti-cancer potential. Although the clinical use of 3, 3′-Diindolylmethane (DIM) has been established, its low chemical stability and bioavailability, limits its therapeutic applications. Increasing effort has been undertaken to improve DIM’s biological activity including nanoformulations. Here, we evaluated the efficacy of DIM nanoparticles (DIM-NPs) coated with PEG/chitosan for the treatment of liver cancer and elucidated the underlying molecular mechanisms contributing to its anti-tumor activity. DIM-PLGA-PEG/chitosan NPs were synthesized and characterized using dynamic light scattering (DLS). The effect of newly synthesized DIM-NPs was evaluated in HepG-2 and HUH-7 hepatocarcinoma cells and compared to THLE-2 immortal normal liver cells and WI-38 (normal lung fibroblast cells). These cells were treated with different non-cytotoxic concentrations of DIM-NPs and MTT assay and other functional assays were performed. Compared to normal cells, DIM-NPs induced cytotoxicity in HepG-2 cells at 6.25 µg/mL after 48 h of treatment. Treatment of HepG-2 cells with the 50 % inhibitory concentration (IC50) 12.5 µg/mL of DIM-NPs inhibited cell migration (p < 0.001). Treatment of chicken embryo with 5ug/ml DIM-NPs reduced (p < 0.001) angiogenesis at day 4. Notably, at the molecular level, DIM-NPs upregulated Bax and p53 and downregulated Bcl-2 in a dose-dependent manner. DIM-NPs also induced cell apoptosis in HepG-2 cells. Treatment of hepatic cells with DIM-NPs decreased cell proliferation, migration and angiogenesis, and induced cell death via up-regulation of Bax and p53, and down-regulation of Bcl-2 in HepG-2 cells. Further investigations are necessitated to determine the pharmacokinetics of DIM-NPs using a preclinical cancer model.http://www.sciencedirect.com/science/article/pii/S10183647230032693, 3′-Diindolylmethane (DIM) nanoparticlesHepatic cancer cellsMigrationAngiogenesisApoptosis |
| spellingShingle | Steve Harakeh Saber H. Saber Turki alamri Rajaa Al-Raddadi Soad Al-Jaouni Hanaa Tashkandi Mohammed Qari Yousef Qari Isaac O. Akefe Zakariya Y. Abd Elmageed Shafiul Haque Anwar M Hashem Eram Albajri Shaker Mousa Novel 3′-diindolylmethane nanoformulation induces apoptosis, and reduces migration and angiogenesis in liver cancer cells Journal of King Saud University: Science 3, 3′-Diindolylmethane (DIM) nanoparticles Hepatic cancer cells Migration Angiogenesis Apoptosis |
| title | Novel 3′-diindolylmethane nanoformulation induces apoptosis, and reduces migration and angiogenesis in liver cancer cells |
| title_full | Novel 3′-diindolylmethane nanoformulation induces apoptosis, and reduces migration and angiogenesis in liver cancer cells |
| title_fullStr | Novel 3′-diindolylmethane nanoformulation induces apoptosis, and reduces migration and angiogenesis in liver cancer cells |
| title_full_unstemmed | Novel 3′-diindolylmethane nanoformulation induces apoptosis, and reduces migration and angiogenesis in liver cancer cells |
| title_short | Novel 3′-diindolylmethane nanoformulation induces apoptosis, and reduces migration and angiogenesis in liver cancer cells |
| title_sort | novel 3 diindolylmethane nanoformulation induces apoptosis and reduces migration and angiogenesis in liver cancer cells |
| topic | 3, 3′-Diindolylmethane (DIM) nanoparticles Hepatic cancer cells Migration Angiogenesis Apoptosis |
| url | http://www.sciencedirect.com/science/article/pii/S1018364723003269 |
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