Kamran, Sareh and Sinniah, Ajantha and Chik, Zamri and Nelli, Giribabu and Alshawsh, Mohammed Abdullah (2024) Synergistic anti-tumorigenic effect of diosmetin in combination with 5-fluorouracil on human colon cancer xenografts in nude mice. Biochemical and Biophysical Research Communications, 735. ISSN 0006-291X, DOI https://doi.org/10.1016/j.bbrc.2024.150677.
Full text not available from this repository.Abstract
5-Fluorouracil (5-FU) is frequently used to treat colorectal cancer (CRC), but its clinical application is limited by its toxicity. Natural compounds have been combined with chemotherapeutic drugs to reduce chemotherapy-related toxicity. Diosmetin, a natural flavonoid, has demonstrated anticancer effects against CRC. This study investigated diosmetin's potential in combination with 5-FU using a murine model of HCT-116 colon cancer xenografts in nu/nu nude mice. HCT-116 cells were injected into the right flanks of mice, and once tumors reached a size of 50 mm(3), the mice were treated with diosmetin (100 mg/kg), 5-FU (30 mg/kg), or a combination of both at two dose levels (100 + 30 mg/kg and 50 + 15 mg/kg) for 4 weeks. Blood and tumors were collected on the final day for further analysis. Mice treated with the higher combination dose exhibited the smallest tumor volume (330.91 +/- 88.49 mm(3)). Biochemistry and histology analysis showed no toxicity or abnormalities in the liver, kidney, and heart with the combination therapy. Immunohistochemistry results revealed a notable reduction in the proliferation marker (Ki67) and inflammation marker (TLR4) in tumors from high-dose combination-treated mice. Moreover, immunofluorescence data indicated increased levels of apoptotic markers (Bax, Caspase-3, p53, p21) and downregulation of anti-apoptotic protein (Bcl-2) in the high-dose combination group. The findings suggest that 100 mg/kg of diosmetin combined with 30 mg/kg 5-FU significantly reduced tumor volume and had a less toxic effect on the heart compared to 5-FU monotherapy.
| Item Type: | Article |
|---|---|
| Funders: | Ministry of Higher Education, Malaysia [Grant no. FP103-2019, FRGS/1/2019/SKK10/UM/02/3] |
| Uncontrolled Keywords: | Colon cancer; Diosmetin; 5-Fluorouracil; Synergistic effect; Xenograft tumor |
| Subjects: | R Medicine |
| Divisions: | Faculty of Medicine > Department of Pharmacology Faculty of Medicine > Physiology Department |
| Depositing User: | Ms. Juhaida Abd Rahim |
| Date Deposited: | 22 Oct 2025 01:45 |
| Last Modified: | 22 Oct 2025 01:45 |
| URI: | http://eprints.um.edu.my/id/eprint/46492 |
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