JCHOR
Journal of Current Hematology & Oncology Research

The Journal of Current Hematology & Oncology Research regularly publishes internationally qualified research in hematology and oncology within the current scholarly knowledge. This journal is indexed by indices that are considered international scientific journal indices (DRJI, ESJI, OAJI, etc.). According to the current Associate Professorship criteria, it is within the scope of International Article 1-d. Each article published in this journal corresponds to 5 points.

eISSN: 2980-0854
Creative Commons CC BY-NC-ND 4.0 International License.
EndNote Style

Online Manuscript System

Index
Original Article
Determination of the therapeutic effects of apigenin on chronic myeloid leukemia stem cells; a mechanistic approach
Abstract
Aims: Chronic myeloid leukemia (CML) is a type of leukemia characterized by the Philadelphia (Ph) chromosome encoding the BCR-ABL protein. Significant success has been achieved in the treatment of CML with the development of agents that target this protein and inhibit its activity, but the resistance that develops in patients against these drugs limits absolute success. One of the main reasons for the resistance problem is the ineffectiveness of current therapies for CML stem cells. Apigenin (4',5,7- trihydroxyflavone) is a flavanoid found in various vegetables and fruits and has the effects of suppressing proliferation and inducing apoptosis in different cancer types. In this study, we aimed to determine the therapeutic potential of apigenin on K562 CML stem cells.
Methods: The effects of apigenin on the proliferation of K562 CML stem cells were determined by an XTT cell proliferation assay. Apoptotic effects of apigenin on K562 CML stem cells were determined by changes in mitochondrial membrane potential (MZP), caspase-3 enzyme activity, and the Annexin-V method using flow cytometry.
Results: The proliferation of K562 CML stem cells exposed to increasing doses of Apigenin (1-40 nM) for 48 hours decreased dose-dependently, and the IC50 value of Apigenin was calculated at 3 nM. Compared to the control group, an increase in caspase-3 enzyme activity was calculated in stem cells treated with apigenin at the same doses. Disruptions in the mitochondrial membrane potential of Apigenin-treated CML stem cells and Annexin-V assay results also showed that Apigenin dose-dependently induced apoptosis and caused significant increases in the apoptotic cell population.
Conclusion: It was shown for the first time in this study that apigenin may have therapeutic effects on CML stem cells. It was determined that this effect of apigenin was achieved by triggering caspase-3 enzyme activity and disruptions in the mitochondrial membrane.

Keywords : Apigenin, chronic myeloid leukemia stem cells, apoptosis, cytotoxicity

Download Article


1. Samadian N, Hashemi M. Effects of apigenin and apigenin- loadednanogel on induction of apoptosis in human chronic myeloid leukemiacells. Galen Med J. 2018;7:e1008.
2. Bhamidipati PK, Kantarjian H, Cortes J, Cornelison AM, JabbourE. Management of imatinib-resistant patients with chronic myeloidleukemia.Ther Adv Hematol.2013;4(2):103-117.
3. Mahbub A, Le Maitre C, Haywood-Small S, Cross N, Jordan-MahyN. Polyphenols act synergistically with doxorubicin and etoposide inleukaemia cell lines.Cell Death Discov.2015;1(1):15043-15055.
4. Qinghong S, Shen G, Lina S, et al. Comparative proteomics analysisof differential proteins in respond to doxorubicin resistance inmyelogenous leukemia cell lines.Proteome Sci.2015;13(1):1-12.
5. Sak K, Everaus H. Established human cell lines as models to study anti-leukemic effects of flavonoids.Curr Genomics.2017;18(1):3-26.
6. Li Y, Wang H, Zhang R, Zhang G, Yang Y, Liu Z. Biofabrication ofpolyphenols coated Nano palladium and its in-vitro cytotoxicityagainst human leukemia cell lines (K562).J Photochem PhotobiolB.2017;175:173-177.
7. Francesco E, Sotgia F, Lisanti M. Cancer stem cells (CSCs):metabolic strategies for their identification and eradication.BiochemJ.2018;475(9):1611-1634.
8. Jiang Y, Xu P, Dai H. CD33, CD96 and death association protein kinasexpression is associated with the survival rate and/ or response to thechemotherapy in the patients with acute myeloid leukemia.Int Med JExp Clin Res.2017;23:1725-1732.
9. Jiang Z, Wu D, Lin S, Li P. CD34 and CD38 are prognostic biomarkersfor acute B lymphoblastic leukemia.Biomark Res.2016;4:23-37.
10. Yehia S, Abdel-Salam IM, Elgamal BM, El-Agamy B, Hamdy GM,Aldouski HM. Cytotoxic and apoptotic effects of luffa cylindrica leavesextract against acute lymphoblastic leukemic stem cells.Asian Pac JCancer Prev. 2020;21(12):3661-3668.
11. Salehi B, Venditti A, Sharifi-Rad M, et al. The therapeutic potential ofapigenin. Int J Molec Sci. 2019;20(6):1305.
12. Imran M, Gondal TA, Atif M, et al. Apigenin as an anticancer agent.Phytother Res. 2020;34(8):1812-1828.
13. Cardenas H, Arango D, Nicholas C, et al. Dietary apigenin exertsimmune-regulatory activity in vivo by reducing NF-kappaB activity,halting leukocyte infiltration and restoring normal metabolic function.Int J Mol Sci. 2016;17(3):323.
14. Yan X, Qi M, Li P, Zhan Y, Shao H.Apigenin in cancer therapy: anti-cancer effects and mechanisms of action.Cell Biosci. 2017;7:50.
15. Pashaei R. Features of apigenin, luteolin, hesperetin and naringenin incrop and body.Nutr Diet.2016;5(5):300-304.
16. Gencer EB, Ural AU, Avcu F, Baran Y. A novel mechanism of dasatinib-induced apoptosis in chronic myeloid leukemia; ceramide synthase andceramide clearance genes. Ann Hematol. 2011; 90(11):1265-1275.
17. Baran Y, Salas A, Senkal CE, et al. Alterations of ceramide/sphingosine1-phosphate rheostat involved in the regulation of resistance toimatinib-induced apoptosis in K562 human chronic myeloid leukemiacells. J Biologic Chem. 2007;282:10922-10934.
18. Kurosu T, Wu N, Oshikawa G, Kagechika H, Miura O. Enhancementof imatinib-induced apoptosis of BCR/ABL-expressing cells by nutlin-3through synergistic activation of the mitochondrial apoptotic pathway.Apoptosis. 2010;15(5):608-620.
19. Iwasaki R, Ito K, Ishida T, et al. Catechin, green tea component, causescaspase-independent necrosis-like cell death in chronic myelogenousleukemia. Cancer Sci. 2009;100(2):349-356.
20. Patel D, Shukla S, Gupta S. Apigenin and cancer chemoprevention:progress, potential and promise. Int J Oncol. 2007;30(1):233-245.
21. Kang MH, Reynolds CP. Bcl-2 inhibitors: targeting mitochondrialapoptotic pathways in cancer therapy. Clin Cancer Res. 2009;15(4):1126-1132.
22. Arisan ED, Kutuk O, Tezil T, Bodur C, Telci D, Basaga H. Smallinhibitor of Bcl-2, HA14-1, selectively enhanced the apoptotic effect ofcisplatin by modulating Bcl-2 family members in MDA-MB-231 breastcancer cells. Breast Canc Res Treat. 2010;119(2):271-281.
23. Pellicano F, Simara P, Sinclair A, et al. The MEK inhibitor PD184352enhances BMS-214662- induced apoptosis in CD34+ CML stem/progenitor cells. Leukemia. 2011;25(7):1159-1167.
24. Cheng ZY, Liang WT, Niu ZY, Xue F, Yao L, Pan L. Effects of wild typePTEN gene on proliferation, apoptosis and the influence on apoptosiskey factor Bcl-2 and Caspase family on K562 cells. Sichuan Da Xue XueBao Yi Xue Ban=J Sichuan Univ Med Sci Ed. 2009;40(4):679-683.
25. Nica AF, Tsao CC, Watt JC, et al. Ceramide promotes apoptosis inchronic myelogenous leukemia derived K562 cells by a mechanisminvolving caspase-8 and JNK. Cell Cycle. 2008;7(21):3362-3370.
Article available in :
Volume 2, Issue 2, 2024
Page : 24-27
https://doi.org/10.51271/JCHOR-0032
Article Information
Received : 16 Oca 2024
Accepted : 21 Şub 2024
Published : 14 May 2024
Corresponding Author :

Ali Ünal: Division of Hematology, Department of Internal Medicine, Faculty of Medicine, Erciyes University, Kayseri, Turkey

[email protected]
Citation : Ünal A, Göktepe Ö, Çetinkaya M, Baran Y. Determination of the therapeutic effects of apigenin on chronic myeloid leukemia stem cells; a mechanistic approach. J Curr Hematol Oncol Res. 2024;2(2):24-27.

Read: 392
Cited: 0
Download : 50
_Footer