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5-fluorouracil in combination with calcium carbonate nanoparticles loaded with antioxidant thymoquinone against colon cancer: synergistically therapeutic potential and underlying molecular mechanism


Citation

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

Abstract

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.


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Additional Metadata

Item Type: Article
Divisions: Faculty of Veterinary Medicine
Institute of Bioscience
DOI Number: https://doi.org/10.3390/antiox13091030
Publisher: Multidisciplinary Digital Publishing Institute
Keywords: 5-fluorouracil; Colon cancer; Molecular therapeutic mechanisms; Synergistically therapeutic effects; Synthesis and characterization; Thymoquinone-loaded calcium carbonate nanoparticles
Depositing User: Ms. Che Wa Zakaria
Date Deposited: 02 May 2025 07:54
Last Modified: 02 May 2025 07:54
Altmetrics: http://www.altmetric.com/details.php?domain=psasir.upm.edu.my&doi=10.3390/antiox13091030
URI: http://psasir.upm.edu.my/id/eprint/117226
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