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:: Volume 29, Issue 6 (Scientific Journal of Kurdistan University of Medical Sciences 2025) ::
SJKU 2025, 29(6): 1-12 Back to browse issues page
Cytotoxic Effects of Silibinin in Combination with 5-Fluorouracil on HT29 Colorectal Cancer Cells
Bahman Moradi Poodeh
Associate Professor, Department of Laboratory Sciences, Lahijan Branch, Islamic Azad University, Lahijan, Iran & Associate Professor, Department of Laboratory Sciences, Lahijan Branch, Islamic Azad University, Lahijan, Iran , bmoradipoodeh@ahoo.com
Abstract:   (848 Views)
Background and Aim: Colorectal cancer is one of the most common types of cancer in the world, causing many deaths worldwide each year. 5-Fluorouracil is the first choice for the treatment of this type of cancer. Drug resistance and its many side effects are among the weaknesses of this drug. Silibinin, the main bioactive component of silymarin, is originally extracted from Silybum marianum, which is commonly used as an anti-hepatic agent. In recent years, the anticancer effect of silibinin has been observed on different cancer cells. This study aimed to investigate the combined cytotoxic effects of silibinin and 5-fluorouracil on cell viability and p53 expression in the colon cancer HT29 cell line.
Material and Methods: Survival of HT29 cells was evaluated by the MTT method after 48 hours of treatment with different concentrations of silibinin and 5 fluorouracil alone and in combination. The expression level of the P53 protein was measured by Western blot method.
Results: Silibinin and 5-fluorouracil significantly inhibited HT29 cell survival in a dose-dependent manner. The simultaneous use of silibinin and 5-fluorouracil showed that silibinin enhances the cytotoxic effects of 5-fluorouracil. In addition, 100 μg/ml silibinin enhanced the impact of 100 μM 5-fluorouracil on P53 protein expression.
Conclusion: This study suggested that silibinin-5-fluorouracil combination may be a valuable candidate for colon cancer patients. Of course, further studies are needed to reach definitive conclusion.



 
Keywords: Colorectal cancer, Silibinin, 5-fluorouracil, P53 protein, HT29 cell line
Full-Text [PDF 531 kb]   (112 Downloads)    
Type of Study: Original Research | Subject: Molecular Medicine and Genetics
Received: 2024/01/18 | Accepted: 2024/06/24 | Published: 2025/03/9
References
1. 1. Biller LH, Schrag D. Diagnosis and treatment of metastatic colorectal cancer: a review. Jama. 2021;325(7):669-85. [DOI:10.1001/jama.2021.0106] [PMID]
2. Xi Y, Xu P. Global colorectal cancer burden in 2020 and projections to 2040. Transl Oncol. 2021;14(10):101174. [DOI:10.1016/j.tranon.2021.101174] [PMID] []
3. Alizadeh-Navaei R. The Effect of Statins in Combination with Chemotherapy on Colon Cancer Cell Lines. JBUMS. 2022;24(1):50-5.
4. Moutabian H, Majdaeen M, Ghahramani-Asl R, Yadollahi M, Gharepapagh E, Ataei G, et al. A systematic review of the therapeutic effects of resveratrol in combination with 5-fluorouracil during colorectal cancer treatment: With a special focus on the oxidant, apoptotic, and anti-inflammatory activities. Cancer Cell Int. 2022;22(1):1-14. [DOI:10.1186/s12935-022-02561-7] [PMID] []
5. Vodenkova S, Buchler T, Cervena K, Veskrnova V, Vodicka P, Vymetalkova V. 5-fluorouracil and other fluoropyrimidines in colorectal cancer: Past, present and future. P&T. 2020;206:107447. 6.Moracci L, Sensi F, Biccari A, Crotti S, Gaio E, Benetti F, et al. An investigation on [5 fluorouracil and epigallocatechin-3-gallate] complex activity on HT-29 cell death and its stability in gastrointestinal fluid. Oncotarget. 2022;13:476. [DOI:10.18632/oncotarget.28207] [PMID] []
6. Sanaei A, Mohammadzadeh G, Rashidi M. Quercetin Improves the Anti-angiogenic Property of 5-Fluorouracil on the Human Umbilical Vein Endothelial Cells HUVEC Cell Line. Int. J. Cancer Manag.2022;15.4. [DOI:10.5812/ijcm-120315]
7. Aiello P, Sharghi M, Mansourkhani SM, Ardekan AP, Jouybari L, Daraei N, et al. Medicinal plants in the prevention and treatment of colon cancer. Oxidative Med. Cell. 2019;2019. [DOI:10.1155/2019/2075614] [PMID] []
8. Fernández J, Silván B, Entrialgo-Cadierno R, Villar CJ, Capasso R, Uranga JA, et al. Antiproliferative and palliative activity of flavonoids in colorectal cancer. Biomedicine & Pharmacotherapy. 2021;143:112241. [DOI:10.1016/j.biopha.2021.112241] [PMID]
9. Motafeghi F, Shokrzadeh M, Mohammadi H, Shokrzadeh S, Razaghi H. Evaluation of Antibacterial Properties and Cytotoxicity of Ethanolic Extract of Alhagi Maurorum. JBUMS. 2023;25(1):340-7.
10. Wu Z, Tan B, Liu Y, Dunn J, Martorell Guerola P, Tortajada M, et al. Chemical composition and antioxidant properties of essential oils from peppermint, native spearmint and scotch spearmint. Molecules. 2019;24(15):2825. [DOI:10.3390/molecules24152825] [PMID] []
11. Rodríguez LGR, Gasga VMZ, Pescuma M, Van Nieuwenhove C, Mozzi F, Burgos JAS. Fruits and fruit by-products as sources of bioactive compounds. Benefits and trends of lactic acid fermentation in the development of novel fruit-based functional beverages. Int. Food Res. 2021;140:109854. [DOI:10.1016/j.foodres.2020.109854] [PMID]
12. El-Saber Batiha G, Magdy Beshbishy A, G. Wasef L, Elewa YH, A. Al-Sagan A, Abd El-Hack ME, et al. Chemical constituents and pharmacological activities of garlic (Allium sativum L.): A review. Nutrients. 2020;12(3):872. [DOI:10.3390/nu12030872] [PMID] []
13. Boojar MMA, Boojar MMA, Golmohammad S. Overview of Silibinin anti-tumor effects. J. Herb. Med. 2020;23:100375. [DOI:10.1016/j.hermed.2020.100375]
14. Firouzi J, Sotoodehnejadnematalahi F, Shokouhifar A, Rahimi M, Sodeifi N, Sahranavardfar P, et al. Silibinin exhibits anti-tumor effects in a breast cancer stem cell model by targeting stemness and induction of differentiation and apoptosis. BioImpacts: BI. 2022;12(5):415. [DOI:10.34172/bi.2022.23336] [PMID] []
15. Nagy Á, Munkácsy G, Győrffy B. Pancancer survival analysis of cancer hallmark genes. Sci. Rep. 2021;11(1):6047. [DOI:10.1038/s41598-021-84787-5] [PMID] []
16. Gupta A, Shah K, Oza MJ, Behl T. Reactivation of p53 gene by MDM2 inhibitors: a novel therapy for cancer treatment. Biomedicine & Pharmacotherapy. 2019;109:484-92. [DOI:10.1016/j.biopha.2018.10.155] [PMID]
17. Sadia H, Bhinder MA, Irshad A, Zahid B, Ahmed R, Ashiq S, et al. Determination of expression profile of p53 gene in different grades of breast cancer tissues by real time PCR. Afr. Health Sci. 2020;20(3):1273-82. [DOI:10.4314/ahs.v20i3.32] [PMID] []
18. Liebl MC, Hofmann TG. The role of p53 signaling in colorectal cancer. Cancers. 2021;13(9):2125. [DOI:10.3390/cancers13092125] [PMID] []
19. Li H, Zhang J, Tong JHM, Chan AWH, Yu J, Kang W, et al. Targeting the oncogenic p53 mutants in colorectal cancer and other solid tumors. Int. J. Mol. Sci. 2019;20(23):5999. [DOI:10.3390/ijms20235999] [PMID] []
20. Krasteva N, Georgieva M. Promising therapeutic strategies for colorectal cancer treatment based on nanomaterials. Pharmaceutics. 2022;14(6):1213. [DOI:10.3390/pharmaceutics14061213] [PMID] []
21. Shafabakhsh R, Asemi Z. Quercetin: a natural compound for ovarian cancer treatment. J. Ovarian Res. 2019;12:1-9. [DOI:10.1186/s13048-019-0530-4] [PMID] []
22. Sauter ER. Cancer prevention and treatment using combination therapy with natural compounds. Expert Rev. Clin. Pharmacol. 2020;13(3):265-85. [DOI:10.1080/17512433.2020.1738218] [PMID]
23. Moradipoodeh B. Amygdalin may potentiate the effects of lapatinib on SK-BR-3 cancer cell death through increasing Bax expression. SJKU 2023, 28(3): 1-12. [DOI:10.61186/sjku.28.3.1]
24. Tewari D, Patni P, Bishayee A, Sah AN, Bishayee A, editors. Natural products targeting the PI3K-Akt-mTOR signaling pathway in cancer: A novel therapeutic strategy. Semin Cancer Biol . 2022:80:1-17 [DOI:10.1016/j.semcancer.2019.12.008] [PMID]
25. Ismail NI, Othman I, Abas F, H. Lajis N, Naidu R. Mechanism of apoptosis induced by curcumin in colorectal cancer. Int. J. Mol. Sci. 2019;20(10):2454. [DOI:10.3390/ijms20102454] [PMID] []
26. Xie Y-H, Chen Y-X, Fang J-Y. Comprehensive review of targeted therapy for colorectal cancer. Signal Transduct Target Ther. 2020;5(1):22. [DOI:10.1038/s41392-020-0116-z] [PMID] []
27. Shin MH, Kim J, Lim SA, Kim J, Lee K-M. Current insights into combination therapies with MAPK inhibitors and immune checkpoint blockade. Int. J. Mol. Sci. 2020;21(7):2531. [DOI:10.3390/ijms21072531] [PMID] []
28. Si L, Liu W, Hayashi T, Ji Y, Fu J, Nie Y, et al. Silibinin-induced apoptosis of breast cancer cells involves mitochondrial impairment. Arch. Biochem. 2019;671:42-51. [DOI:10.1016/j.abb.2019.05.009] [PMID]
29. 30 Iyengar RM, Devaraj E. Silibinin triggers the mitochondrial pathway of apoptosis in human Oral squamous carcinoma cells. APJCP. 2020;21(7):1877. [DOI:10.31557/APJCP.2020.21.7.1877] [PMID] []
30. Sameri S, Saidijam M, Bahreini F, Najafi R. Cancer chemopreventive activities of silibinin on colorectal cancer through regulation of E-cadherin/β-catenin pathway. Nutr Cancer. 2021;73(8):1389-99. [DOI:10.1080/01635581.2020.1800764] [PMID]
31. Jackson K, Devaraj E, Lakshmi T, Rajeshkumar S, Dua K, Chellappan DK, et al. Cytotoxic potentials of silibinin assisted silver nanoparticles on human colorectal HT-29 cancer cells. Bioinformation. 2020;16(11):817. [DOI:10.6026/97320630016817] [PMID] []
32. Zare Z, Lohrasbi A, Sheikhalishahi ZS, Asadi A, Zakeri M, Hosseinabadi F, et al. Silibinin inhibits TGF-β-induced MMP-2 and MMP-9 through Smad Signaling pathway in colorectal cancer HT-29 cells. Clin. Cancer Res. 2020. [DOI:10.18502/bccr.v12i2.5752]
33. Fallah M, Davoodvandi A, Nikmanzar S, Aghili S, Mirazimi SMA, Aschner M, et al. Silymarin (milk thistle extract) as a therapeutic agent in gastrointestinal cancer. Biomedicine & Pharmacotherapy. 2021;142:112024. [DOI:10.1016/j.biopha.2021.112024] [PMID] []
34. Michel M, Kaps L, Maderer A, Galle PR, Moehler M. The role of p53 dysfunction in colorectal cancer and its implication for therapy. Cancers. 2021;13(10):2296. [DOI:10.3390/cancers13102296] [PMID] []
35. Koushki M, Khedri A, Aberomand M, Baghbani KA, Mohammadzadeh G. Synergistic anti-cancer effects of silibinin-etoposide combination against human breast carcinoma MCF-7 and MDA-MB-231 cell lines. Iran. J. Basic Med. Sci. 2021;24(9):1211.
36. Patel S, Waghela B, Shah K, Vaidya F, Mirza S, Patel S, et al. Silibinin, A natural blend in polytherapy formulation for targeting Cd44v6 expressing colon cancer stem cells. Sci. Rep. 2018;8(1):16985. [DOI:10.1038/s41598-018-35069-0] [PMID] []
37. Gupta J, Abdulsahib WK, Jalil AT, Kareem DS, Aminov Z, Alsaikhan F, et al. Prostate cancer and microRNAs: New insights into apoptosis. Pathol Res Pract. 2023;245:154436 [DOI:10.1016/j.prp.2023.154436] [PMID]
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Moradi Poodeh B. Cytotoxic Effects of Silibinin in Combination with 5-Fluorouracil on HT29 Colorectal Cancer Cells. SJKU 2025; 29 (6) :1-12
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Volume 29, Issue 6 (Scientific Journal of Kurdistan University of Medical Sciences 2025) Back to browse issues page
مجله علمی دانشگاه علوم پزشکی کردستان Scientific Journal of Kurdistan University of Medical Sciences
مجله علمی دانشگاه علوم پزشکی کردستان Scientific Journal of Kurdistan University of Medical Sciences
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