Regulatory effects of kaempferol and silymarin on miRNAs and cell cycle/apoptosis pathways in chronic myeloid leukemia cells

Kutay Bulut; Sunde Yılmaz Süslüer

doi:10.18614/dehm.1760340

Regulatory effects of kaempferol and silymarin on miRNAs and cell cycle/apoptosis pathways in chronic myeloid leukemia cells

Abstract

Objective Chronic Myeloid Leukemia (CML) is a myeloproliferative disorder characterized by the BCR-ABL fusion gene, which leads to constitutive tyrosine kinase activity and results in uncontrolled cell proliferation. This genetic alteration causes increased cell growth and suppression of apoptosis. The aim of this study is to investigate the effects of the natural compounds silymarinand kaempferol on the expression of 88 cancer-related miRNAs and genes associated with apoptosis and cell cycle regulation in the K562 CML cell line. Methods K562 cells were treated with the IC₅₀ doses of silymarin and kaempferol for 48 hours. Following total RNA (including miRNA) isolation, the expression levels of 88 miRNAs as well as apoptosis- and cell cycle-related genes were evaluated using quantitative PCR. Expression changes were analyzed using the 2^-ΔΔCT method, and fold changes ≥2 or ≤−2 were considered statistically significant (p<0.05). Results Both compounds significantly altered the expression of several miRNAs. Tumor-suppressor miRNAs were generally upregulated, while oncogenic miRNAs such as miR-21 were downregulated. Among apoptosis-related genes, CASP3, BAX and TP53 were upregulated, whereas BCL2 was downregulated. Additionally, cell cycle regulatory genes such as CDK1 and CCNB1 were also found to be downregulated. Conclusion Kaempferol and silymarin exhibited anticancer potential in CML by modulating miRNA profiles and regulating genes involved in apoptosis and cell cycle processes. These findings suggest that both compounds may serve as potential adjunct therapeutic agents in the treatment of Chronic Myeloid Leukemia.

Keywords

References

1. Melo JV, Hughes TP, Apperley JF. Chronic myeloid leukemia. ASH Education Program Book. 2003:132–152.
2. Kang ZJ, Liu YF, Xu LZ, Long ZJ, Huang D, Yang Y, et al. The Philadelphia chromosome in leukemogenesis. Chin J Cancer. 2016;35:48.
3. O'Brien SG, Guilhot F, Larson RA, Gathmann I, Baccarani M, Cervantes F, et al. Imatinib compared with interferon and low-dose cytarabine for newly diagnosed chronic-phase chronic myeloid leukemia. N Engl J Med. 2003;348(11):994–1004.
4. Garcia-Gutierrez JV, Herrera P, Abalo LL, Rey MD, Calbacho M, Ramos L, et al. Impact of second-generation tyrosine kinase inhibitors as second-line treatment for patients with chronic myeloid leukemia. Blood. 2011;118:632.
5. Eskazan AE, Ayer M, Kantarcioglu B, Arica D, Demirel N, Aydin D, et al. First-line treatment of chronic phase chronic myeloid leukaemia patients with the generic formulations of imatinib mesylate. Br J Haematol. 2014;167(1):139–141.
6. Havsteen BH. The biochemistry and medical significance of the flavonoids. Pharmacol Ther. 2002;96(2–3):67–202.
7. Alrumaihi F, Almatroodi SA, Alharbi HOA, Alwanian WM, Alharbi FA, Almatroudi A, et al. Pharmacological potential of kaempferol, a flavonoid in the management of pathogenesis via modulation of inflammation and other biological activities. Molecules. 2024;29(9):2007.
8. Chen Y, Fu LL, Wen X, Liu B, Huang J, Wang JH, et al. Oncogenic and tumor suppressive roles of microRNAs in apoptosis and autophagy. Apoptosis. 2014;19(8):1177–1189.

9. Pfeffer S, Zavolan M, Grässer FA, Chien M, Russo JJ, Ju J, et al. Identification of virus-encoded microRNAs. Science. 2004;304(5671):734–736.
10. Saller R, Melzer J, Reichling J, Brignoli R, Meier R. An updated systematic review of the pharmacology of silymarin. Forsch Komplement. 2007;14:70–80.
11. Wadhwa K, Pahwa R, Kumar M, Kumar S, Sharma PC, Singh G, et al. Mechanistic insights into the pharmacological significance of silymarin. Molecules. 2022;27:5327.
12. Neha, Jaggi A, Singh N. Silymarin and its role in chronic diseases. Advances in Experimental Medicine and Biology. Berlin/Hamburg: Springer; 2016. Vol. 929. p. 25–44.
13. Periferakis A, Periferakis K. On the dissemination of acupuncture to Europe. JournalNX. 2020;6:201–209.
14. Neuhouser ML. Dietary flavonoids and cancer risk: Evidence from human population studies. Nutr Cancer. 2004;50:1–7.
15. Di Bacco A, Keeshan K, McKenna SL, Cotter TG. Molecular abnormalities in chronic myeloid leukemia: deregulation of cell growth and apoptosis. Oncologist. 2000;5(5):405–415.
16. Weng CJ, Yen GC. Flavonoids, a ubiquitous dietary phenolic subclass, exert extensive in vitro anti-invasive and in vivo anti-metastatic activities. Cancer Metastasis Rev. 2012;31:323–351.
17. Zamora-Ros R, Sacerdote C, Ricceri F, Weiderpass E, Roswall N, Buckland G, et al. Flavonoid and lignan intake in relation to bladder cancer risk in the European Prospective Investigation into Cancer and Nutrition (EPIC) study. Br J Cancer. 2014;111:1870–1880.
18. Petrick JL, Steck SE, Bradshaw PT, Trivers KF, Abrahamson PE, Engel LS, et al. Dietary intake of flavonoids and oesophageal and gastric cancer: Incidence and survival in the United States of America (USA). Br J Cancer. 2015;112:1291–1300.
19. Kayabasi C, Caner A, Susluer SY, Okcanoglu TB, Yelken BO, Asik A, et al. Comparative expression analysis of dasatinib- and ponatinib regulated lncRNAs in chronic myeloid leukemia and their network analysis. Med Oncol. 2022;39:29.

Details

Primary Language

English

Subjects

Medical Genetics (Excl. Cancer Genetics)

Journal Section

Research Article

Authors

Kutay Bulut This is me
Türkiye

Sunde Yılmaz Süslüer ^*
0000-0002-0535-150X
Türkiye

Early Pub Date

April 29, 2026

Publication Date

April 29, 2026

Submission Date

August 7, 2025

Acceptance Date

December 23, 2025

Published in Issue

Year 2026 Volume: 40 Number: 2

DOI

https://doi.org/10.18614/dehm.1760340

IZ

https://izlik.org/JA23LG56KK

Cite

RIS / Bibtex

APA

Bulut, K., & Yılmaz Süslüer, S. (2026). Regulatory effects of kaempferol and silymarin on miRNAs and cell cycle/apoptosis pathways in chronic myeloid leukemia cells. Developments and Experiments in Health and Medicine, 40(2), 184-198. https://doi.org/10.18614/dehm.1760340

AMA

1.Bulut K, Yılmaz Süslüer S. Regulatory effects of kaempferol and silymarin on miRNAs and cell cycle/apoptosis pathways in chronic myeloid leukemia cells. Dev Exp Health Med. 2026;40(2):184-198. doi:10.18614/dehm.1760340

Chicago

Bulut, Kutay, and Sunde Yılmaz Süslüer. 2026. “Regulatory Effects of Kaempferol and Silymarin on MiRNAs and Cell Cycle Apoptosis Pathways in Chronic Myeloid Leukemia Cells”. Developments and Experiments in Health and Medicine 40 (2): 184-98. https://doi.org/10.18614/dehm.1760340.

EndNote

Bulut K, Yılmaz Süslüer S (April 1, 2026) Regulatory effects of kaempferol and silymarin on miRNAs and cell cycle/apoptosis pathways in chronic myeloid leukemia cells. Developments and Experiments in Health and Medicine 40 2 184–198.

IEEE

[1]K. Bulut and S. Yılmaz Süslüer, “Regulatory effects of kaempferol and silymarin on miRNAs and cell cycle/apoptosis pathways in chronic myeloid leukemia cells”, Dev Exp Health Med, vol. 40, no. 2, pp. 184–198, Apr. 2026, doi: 10.18614/dehm.1760340.

ISNAD

Bulut, Kutay - Yılmaz Süslüer, Sunde. “Regulatory Effects of Kaempferol and Silymarin on MiRNAs and Cell Cycle Apoptosis Pathways in Chronic Myeloid Leukemia Cells”. Developments and Experiments in Health and Medicine 40/2 (April 1, 2026): 184-198. https://doi.org/10.18614/dehm.1760340.

JAMA

1.Bulut K, Yılmaz Süslüer S. Regulatory effects of kaempferol and silymarin on miRNAs and cell cycle/apoptosis pathways in chronic myeloid leukemia cells. Dev Exp Health Med. 2026;40:184–198.

MLA

Bulut, Kutay, and Sunde Yılmaz Süslüer. “Regulatory Effects of Kaempferol and Silymarin on MiRNAs and Cell Cycle Apoptosis Pathways in Chronic Myeloid Leukemia Cells”. Developments and Experiments in Health and Medicine, vol. 40, no. 2, Apr. 2026, pp. 184-98, doi:10.18614/dehm.1760340.

Vancouver

1.Kutay Bulut, Sunde Yılmaz Süslüer. Regulatory effects of kaempferol and silymarin on miRNAs and cell cycle/apoptosis pathways in chronic myeloid leukemia cells. Dev Exp Health Med. 2026 Apr. 1;40(2):184-98. doi:10.18614/dehm.1760340