2022_Artocarpin Suppression of Cancer Stem Cell And Its Stemness Characterization in Non-Small Cell Lung Cancer
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| country | Malaysia |
| date | 2022-09-07 |
| format | General Document |
| id | 15378 |
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| internalnotes | Sila masukkan subject wajib Dissertations, Academic. Terima kasih... |
| originalfilename | ARTOCARPIN SUPPRESSION OF CANCER STEM CELL AND ITS STEMNESS CHARACTERIZATION IN NON-SMALL CELL LUNG CANCER (PHD_2022).pdf |
| person | Nik Nurul Najihah Binti Nik Mat Daud |
| recordtype | oai_dc |
| resourceurl | https://intelek.unisza.edu.my/intelek/pages/view.php?ref=15378 |
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| spelling | 15378 https://intelek.unisza.edu.my/intelek/pages/view.php?ref=15378 https://intelek.unisza.edu.my/intelek/pages/search.php?search=!collection3 General Document Malaysia Library Staff (Top Management) Library Staff (Management) Library Staff (Support) Terengganu Faculty of Medicine English application/pdf 1.5 Server storage Scanned document Universiti Sultan Zainal Abidin UniSZA Private Access Universiti Sultan Zainal Abidin SAMBox 2.3.4; modified using iTextSharp™ 5.5.10 ©2000-2016 iText Group NV (AGPL-version) 277 ARTOCARPIN SUPPRESSION OF CANCER STEM CELL AND ITS STEMNESS CHARACTERIZATION IN NON-SMALL CELL LUNG CANCER (PHD_2022).pdf 2022_Artocarpin Suppression of Cancer Stem Cell And Its Stemness Characterization in Non-Small Cell Lung Cancer Nik Nurul Najihah Binti Nik Mat Daud Copyright©PWB2025 2022-09-07 Artocarpin—Pharmacology Lung cancer is one of the most chronic diseases in the world. The use of chemotherapy as cancer treatment nowadays targeted only proliferating cells with neglecting of a small subset population of cancer stem cells (CSCs) which can still survive and promote cancer relapse aside from its adverse effects. Evidence showing that tumour heterogeneity of CSCs contributes to lung cancer recurrence leading to the difficulty in treating non-small cell lung cancer (NSCLC). Therefore, searching for an alternative in cancer therapy targeting this small subset of the lung cancer population is crucial. Artocarpin, isolated from the heartwoods of Artocarpus heterophyllus has been used for centuries as a medicament to treat numerous ailments, including cancer. As its treatment is increasingly being recognized, the present study sought to investigate the pharmacological effect of artocarpin on CSCs in NSCLC cells. Cell surface markers (CD166 and CD44) were used in this study to isolate lung CSCs from lung adenocarcinoma cells (H460). The cytotoxicity study was done on the isolated cells followed by characterisation of CSCs, which includes cells differentiation and self-renewal capabilities, cellular migration, and invasion. The stemness gene expression of Wnt and β-catenin were analysed using real-time quantitative polymerase chain reaction and molecular docking analysis to evaluate the Wnt/β catenin signalling pathway activity. Graphpad Prism, Image J analysis, and Microsoft Excel were used to analyse the data. 62.5% of CD166+CD44+ cells and 37.5% of CD166-CD44- cells were identified in H460 cells. The results revealed that artocarpin exerted the highest cytotoxic value against lung CSCs with IC50 5.07 µg/mL compared to other compounds. The multipotent characteristic of lung CSCs such as its ability to differentiate into adipogenic, osteogenic, and chondrogenic, showed an altered condition upon the treatment with artocarpin. In addition, artocarpin significantly attenuated the self-renewal capabilities by reducing the colony and sphere formation. This result was similarly observed in the migration and invasion assays. Furthermore, stemness genes expression such as KLF4, SOX2, NANOG, TWIST1, VEGFA, and CCDN1 were found to be reduced in the treated cells with FC value (0.025, 0.104, 0.074, 0.227, 0.220, and 0.124) respectively. Molecular docking analysis was carried out to validate the activity of the artocarpin in suppressing the stemness characteristic of CSCs. The findings showed that artocarpin possessed the best-docked complexes with β-catenin and Wnt protein with high binding energy values (-7.04 kcal/mol and -14.91 kcal/mol) respectively compared to other Wnt/β catenin inhibitors. This finding supports the inhibitory activity of artocarpin on lung CSCs with low Wnt and β-catenin gene expression levels and FC value (0.155 and 0.129). Therefore, based on this study, it is suggested that artocarpin has potential to be developed as therapeutic agent to inhibit stem cell regeneration in NSCLC via the Wnt/β-catenin pathway because it has the lowest inhibitory concentration besides being able to inhibit β-catenin and Wnt protein with high binding energy. The binding of artocarpin to TCF-4 is also a novel finding in this study, where it shows that TCF-4 has the potential to be a therapeutic target in treating lung cancer. Dissertations, Academic Sila masukkan subject wajib Dissertations, Academic. Terima kasih... Artocarpin And Cancer Therapy Cancer Stem Cell Suppression Non-small Cell Lung Cancer (NSCLC) Thesis |
| spellingShingle | 2022_Artocarpin Suppression of Cancer Stem Cell And Its Stemness Characterization in Non-Small Cell Lung Cancer |
| state | Terengganu |
| subject | Artocarpin—Pharmacology Dissertations, Academic |
| summary | Lung cancer is one of the most chronic diseases in the world. The use of chemotherapy as cancer treatment nowadays targeted only proliferating cells with neglecting of a small subset population of cancer stem cells (CSCs) which can still survive and promote cancer relapse aside from its adverse effects. Evidence showing that tumour heterogeneity of CSCs contributes to lung cancer recurrence leading to the difficulty in treating non-small cell lung cancer (NSCLC). Therefore, searching for an alternative in cancer therapy targeting this small subset of the lung cancer population is crucial. Artocarpin, isolated from the heartwoods of Artocarpus heterophyllus has been used for centuries as a medicament to treat numerous ailments, including cancer. As its treatment is increasingly being recognized, the present study sought to investigate the pharmacological effect of artocarpin on CSCs in NSCLC cells. Cell surface markers (CD166 and CD44) were used in this study to isolate lung CSCs from lung adenocarcinoma cells (H460). The cytotoxicity study was done on the isolated cells followed by characterisation of CSCs, which includes cells differentiation and self-renewal capabilities, cellular migration, and invasion. The stemness gene expression of Wnt and β-catenin were analysed using real-time quantitative polymerase chain reaction and molecular docking analysis to evaluate the Wnt/β catenin signalling pathway activity. Graphpad Prism, Image J analysis, and Microsoft Excel were used to analyse the data. 62.5% of CD166+CD44+ cells and 37.5% of CD166-CD44- cells were identified in H460 cells. The results revealed that artocarpin exerted the highest cytotoxic value against lung CSCs with IC50 5.07 µg/mL compared to other compounds. The multipotent characteristic of lung CSCs such as its ability to differentiate into adipogenic, osteogenic, and chondrogenic, showed an altered condition upon the treatment with artocarpin. In addition, artocarpin significantly attenuated the self-renewal capabilities by reducing the colony and sphere formation. This result was similarly observed in the migration and invasion assays. Furthermore, stemness genes expression such as KLF4, SOX2, NANOG, TWIST1, VEGFA, and CCDN1 were found to be reduced in the treated cells with FC value (0.025, 0.104, 0.074, 0.227, 0.220, and 0.124) respectively. Molecular docking analysis was carried out to validate the activity of the artocarpin in suppressing the stemness characteristic of CSCs. The findings showed that artocarpin possessed the best-docked complexes with β-catenin and Wnt protein with high binding energy values (-7.04 kcal/mol and -14.91 kcal/mol) respectively compared to other Wnt/β catenin inhibitors. This finding supports the inhibitory activity of artocarpin on lung CSCs with low Wnt and β-catenin gene expression levels and FC value (0.155 and 0.129). Therefore, based on this study, it is suggested that artocarpin has potential to be developed as therapeutic agent to inhibit stem cell regeneration in NSCLC via the Wnt/β-catenin pathway because it has the lowest inhibitory concentration besides being able to inhibit β-catenin and Wnt protein with high binding energy. The binding of artocarpin to TCF-4 is also a novel finding in this study, where it shows that TCF-4 has the potential to be a therapeutic target in treating lung cancer. |
| title | 2022_Artocarpin Suppression of Cancer Stem Cell And Its Stemness Characterization in Non-Small Cell Lung Cancer |
| title_full | 2022_Artocarpin Suppression of Cancer Stem Cell And Its Stemness Characterization in Non-Small Cell Lung Cancer |
| title_fullStr | 2022_Artocarpin Suppression of Cancer Stem Cell And Its Stemness Characterization in Non-Small Cell Lung Cancer |
| title_full_unstemmed | 2022_Artocarpin Suppression of Cancer Stem Cell And Its Stemness Characterization in Non-Small Cell Lung Cancer |
| title_short | 2022_Artocarpin Suppression of Cancer Stem Cell And Its Stemness Characterization in Non-Small Cell Lung Cancer |
| title_sort | 2022_artocarpin suppression of cancer stem cell and its stemness characterization in non-small cell lung cancer |