5-fluorouracil in combination with calcium carbonate nanoparticles loaded with antioxidant thymoquinone against colon cancer: synergistically therapeutic potential and underlying molecular mechanism
Colon cancer is the third most common cancer worldwide, with high mortality. Adverse side effects and chemoresistance of the first-line chemotherapy 5-fluorouracil (5-FU) have promoted the widespread use of combination therapies. Thymoquinone (TQ) is a natural compound with potent antioxidant activi...
| Main Authors: | , , , , |
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| Format: | Article |
| Language: | English |
| Published: |
Multidisciplinary Digital Publishing Institute
2024
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| Online Access: | http://psasir.upm.edu.my/id/eprint/117226/ http://psasir.upm.edu.my/id/eprint/117226/1/117226.pdf |
| _version_ | 1848867193854361600 |
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| author | Deng, Xi Yang, Zhongming Chan, Kim Wei Ismail, Norsharina Abu Bakar, Md Zuki |
| author_facet | Deng, Xi Yang, Zhongming Chan, Kim Wei Ismail, Norsharina Abu Bakar, Md Zuki |
| author_sort | Deng, Xi |
| building | UPM Institutional Repository |
| collection | Online Access |
| description | Colon cancer is the third most common cancer worldwide, with high mortality. Adverse side effects and chemoresistance of the first-line chemotherapy 5-fluorouracil (5-FU) have promoted the widespread use of combination therapies. Thymoquinone (TQ) is a natural compound with potent antioxidant activity. Loading antioxidants into nano delivery systems has been a major advance in enhancing their bioavailability to improve clinical application. Hence, this study aimed to prepare the optimal TQ-loaded calcium carbonate nanoparticles (TQ-CaCO3 NPs) and investigate their therapeutic potential and underlying molecular mechanisms of TQ-CaCO3 NPs in combination with 5-FU against colon cancer. Firstly, we developed purely aragonite CaCO3 NPs with a facile mechanical ball-milling method. The pH-sensitive and biocompatible TQ-CaCO3 NPs with sustained release properties were prepared using the optimal synthesized method (a high-speed homogenizer). The in vitro study revealed that the combination of TQ-CaCO3 NPs (15 μM) and 5-FU (7.5 μM) inhibited CT26 cell proliferation and migration, induced cell apoptosis and cell cycle arrest in the G0/G1 phase, and suppressed the CT26 spheroid growth, exhibiting a synergistic effect. Finally, network pharmacology and molecular docking results indicated the potential targets and crucial signaling pathways of TQ-CaCO3 NPs in combination with 5-FU against colon cancer. Therefore, TQ-CaCO3 NPs combined with 5-FU could enhance the anti-colon cancer effects of 5-FU with broader therapeutic targets, warranting further application for colon cancer treatment. |
| first_indexed | 2025-11-15T14:32:37Z |
| format | Article |
| id | upm-117226 |
| institution | Universiti Putra Malaysia |
| institution_category | Local University |
| language | English |
| last_indexed | 2025-11-15T14:32:37Z |
| publishDate | 2024 |
| publisher | Multidisciplinary Digital Publishing Institute |
| recordtype | eprints |
| repository_type | Digital Repository |
| spelling | upm-1172262025-05-02T07:54:58Z http://psasir.upm.edu.my/id/eprint/117226/ 5-fluorouracil in combination with calcium carbonate nanoparticles loaded with antioxidant thymoquinone against colon cancer: synergistically therapeutic potential and underlying molecular mechanism Deng, Xi Yang, Zhongming Chan, Kim Wei Ismail, Norsharina Abu Bakar, Md Zuki Colon cancer is the third most common cancer worldwide, with high mortality. Adverse side effects and chemoresistance of the first-line chemotherapy 5-fluorouracil (5-FU) have promoted the widespread use of combination therapies. Thymoquinone (TQ) is a natural compound with potent antioxidant activity. Loading antioxidants into nano delivery systems has been a major advance in enhancing their bioavailability to improve clinical application. Hence, this study aimed to prepare the optimal TQ-loaded calcium carbonate nanoparticles (TQ-CaCO3 NPs) and investigate their therapeutic potential and underlying molecular mechanisms of TQ-CaCO3 NPs in combination with 5-FU against colon cancer. Firstly, we developed purely aragonite CaCO3 NPs with a facile mechanical ball-milling method. The pH-sensitive and biocompatible TQ-CaCO3 NPs with sustained release properties were prepared using the optimal synthesized method (a high-speed homogenizer). The in vitro study revealed that the combination of TQ-CaCO3 NPs (15 μM) and 5-FU (7.5 μM) inhibited CT26 cell proliferation and migration, induced cell apoptosis and cell cycle arrest in the G0/G1 phase, and suppressed the CT26 spheroid growth, exhibiting a synergistic effect. Finally, network pharmacology and molecular docking results indicated the potential targets and crucial signaling pathways of TQ-CaCO3 NPs in combination with 5-FU against colon cancer. Therefore, TQ-CaCO3 NPs combined with 5-FU could enhance the anti-colon cancer effects of 5-FU with broader therapeutic targets, warranting further application for colon cancer treatment. Multidisciplinary Digital Publishing Institute 2024-08-25 Article PeerReviewed text en cc_by_4 http://psasir.upm.edu.my/id/eprint/117226/1/117226.pdf Deng, Xi and Yang, Zhongming and Chan, Kim Wei and Ismail, Norsharina and Abu Bakar, Md Zuki (2024) 5-fluorouracil in combination with calcium carbonate nanoparticles loaded with antioxidant thymoquinone against colon cancer: synergistically therapeutic potential and underlying molecular mechanism. Antioxidants, 13 (9). art. no. 1030. pp. 1-32. ISSN 2076-3921 https://www.mdpi.com/2076-3921/13/9/1030 10.3390/antiox13091030 |
| spellingShingle | Deng, Xi Yang, Zhongming Chan, Kim Wei Ismail, Norsharina Abu Bakar, Md Zuki 5-fluorouracil in combination with calcium carbonate nanoparticles loaded with antioxidant thymoquinone against colon cancer: synergistically therapeutic potential and underlying molecular mechanism |
| title | 5-fluorouracil in combination with calcium carbonate nanoparticles loaded with antioxidant thymoquinone against colon cancer: synergistically therapeutic potential and underlying molecular mechanism |
| title_full | 5-fluorouracil in combination with calcium carbonate nanoparticles loaded with antioxidant thymoquinone against colon cancer: synergistically therapeutic potential and underlying molecular mechanism |
| title_fullStr | 5-fluorouracil in combination with calcium carbonate nanoparticles loaded with antioxidant thymoquinone against colon cancer: synergistically therapeutic potential and underlying molecular mechanism |
| title_full_unstemmed | 5-fluorouracil in combination with calcium carbonate nanoparticles loaded with antioxidant thymoquinone against colon cancer: synergistically therapeutic potential and underlying molecular mechanism |
| title_short | 5-fluorouracil in combination with calcium carbonate nanoparticles loaded with antioxidant thymoquinone against colon cancer: synergistically therapeutic potential and underlying molecular mechanism |
| title_sort | 5-fluorouracil in combination with calcium carbonate nanoparticles loaded with antioxidant thymoquinone against colon cancer: synergistically therapeutic potential and underlying molecular mechanism |
| url | http://psasir.upm.edu.my/id/eprint/117226/ http://psasir.upm.edu.my/id/eprint/117226/ http://psasir.upm.edu.my/id/eprint/117226/ http://psasir.upm.edu.my/id/eprint/117226/1/117226.pdf |