Doxorubicin-induced cell cycle arrest and apoptosis in HL-60 leukemia cells – a narrative review

Authors

  • Dominika Rzeszutek Faculty of Biology, Nature Protection and Sustainable Development, University of Rzeszów, Rzeszów, Poland
  • Ewelina Kuna Faculty of Biology, Nature Protection and Sustainable Development, University of Rzeszów, Rzeszów, Poland https://orcid.org/0000-0002-3203-3195

DOI:

https://doi.org/10.15584/ejcem.2025.4.30

Abstract

Introduction and aim. Doxorubicin is an anthracycline widely used in cancer therapy. Although the complete mechanism of action of doxorubicin is not fully understood, it is known to effectively destroy cancer cells by intercalating into DNA.  This article aims to evaluate the anticancer effect of doxorubicin with particular emphasis on HL-60 leukemia cells and cell cycle/apoptosis.

Material and methods. This narrative review contains a collection and evaluation of peer-reviewed publications on the anticancer properties and therapeutic applications of doxorubicin. It focuses on doxorubicin-induced cell cycle arrest and apoptosis in HL-60 leukemia cells, with particular emphasis on toxicity and resistance. A literature review was conducted using the following databases: PubMed and Google Scholar.

Analysis of the literature. Doxorubicin exhibits potent anticancer activity against many cancer types. Unfortunately, due to serious side effects, primarily related to the cardiotoxicity of the drug, its potential cannot be fully exploited.

Conclusion. In recent years, many approaches have been developed to circumvent the limitations of doxorubicin. Identifying all the pathways of doxorubicin action is important for planning combination therapy, mitigating side effects, and developing new drugs. However, further clinical studies are needed to determine their long-term safety and efficacy.

Downloads

Download data is not yet available.

References

Cieślik A. Epidemiology of leukaemias in Poland. Stud Med. 2011;21(1):53-60.

Wafa A, Moassass F, Liehr T, Al-Ablog A, Al-Achkar W. Acute promyelocytic leukemia with the translocation t(15;17)(q22;q21) associated with t(1;2)(q42~43;q11.2~12): a case report. J Med Case Rep. 2016;10:203. doi:10.1186/s13256-016-0982-8.

Wang Z, Chen Z. Acute promyelocytic leukemia: From highly fatal to highly curable. Blood. 2008;111(5):2505-2515. doi:10.1182/blood-2007-07-102798

Podhorecka M, Macheta A. Acute promyelocytic leukemia - modern approach to disease pathogenesis and differentiation treatment. Postepy Hig Med Dosw (online). 2013;67:1083-1089. doi:10.5604/17322693.1077467

Seferyńska I, Warzocha K. A registry report from the Institute of Hematology and Transfusion Medicine on adult morbidity for acute leukemias between 2004–2010 in Poland made on behalf of the Polish Adult Leukemia Group (PALG). Hematologia. 2014;5(2):162-172. doi: 10.5114/hcp.2014.44988

Sanz MA, Martín G, González M, et al. Risk-adapted treatment of acute promyelocytic leukemia with all-trans-retinoic acid and anthracycline monochemotherapy: A multicenter study by the PETHEMA group. Blood. 2004;103(4):1237-1243. doi:10.1182/blood-2003-07-2462

Saeed S, Logie C, Stunnenberg HG, Martens JH. Genome-wide functions of PML-RARα in acute promyelocytic leukaemia. Br J Cancer. 2011;104(4):554-8. doi: 10.1038/sj.bjc.6606095.

Wierzbowska A. Ostra białaczka szpikowa. Onkol Prakt Klin – Edukacja. 2020;6(A):119-144. doi:10.5603/owpk_edu.70553

Rivankar S. An overview of doxorubicin formulations in cancer therapy. J Cancer Res Ther. 2014;10(4):853-858. doi:10.4103/0973-1482.139267

Johnson-Arbor K, Dubey R. Doxorubicin. In: StatPearls. Treasure Island (FL): StatPearls Publishing; 2023.

Denard B, Lee C, Ye J. Doxorubicin blocks proliferation of cancer cells through proteolytic activation of CREB3L1. eLife. 2012;1:e00090. doi:10.7554/eLife.00090

Patel AG, Kaufmann SH. Cancer: How does doxorubicin work? eLife. 2012;1:e00387. doi:10.7554/eLife.00387

Hou W, Liu Y, Liang H, Wu S. Induction of differentiation of the acute myeloid leukemia cell line HL‑60 by SN3‑L6 and all‑trans retinoic acid. Cell Death Discov. 2020;6:84. doi:10.1038/s41420-020-00354-3

Basu J, Madhulika S, Murmu KC, Mohanty S, Samal P, Das A, Mahapatra S, Saha S, Sinha I, Prasad P. Molecular and epigenetic alterations in normal and malignant myelopoiesis in human leukemia 60 (HL60) promyelocytic cell line model. Front Cell Dev Biol. 2023;11:1060537. doi:10.3389/fcell.2023.1060537.

Sewastianik T, Prochorec-Sobieszek M, Juszczyński P. Deregulation of MYC transcription factor in lymphoid tumors — molecular, pathogenetic, clinical and therapeutic implications. Hematologia. 2012;3(4):313-326.

Reece JB, Urry LA, Cain ML, et al. Campbell Biology. 10th ed. Poznań: Dom Wydawniczy REBIS; 2016:234-249.

Visconti R, Della Monica R, Grieco D. Cell cycle checkpoint in cancer: a therapeutically targetable double‑edged sword. J Exp Clin Cancer Res. 2016;35:153. doi:10.1186/s13046-016-0433-9

Israels ED, Israels LG. The cell cycle. Oncologist. 2000;5(6):510-513. doi:10.1634/theoncologist.5-6-510

Williams GH, Stoeber K. The cell cycle and cancer. J Pathol. 2011;226(2):352-364. doi:10.1002/path.3022

Gąsior Ł, Daszkiewicz R, Michniak K. Role of gamma H2A.X in reproductive cells. Postepy Biol Komór Cell. 2016;43(1):53-72.

Gilewski TA, Dang C, Surbone A, et al. Cytokinetics. In: Bast RC Jr, Kufe DW, Pollock RE, et al., editors. Holland-Frei Cancer Medicine. 5th edition. Hamilton (ON): BC Decker; 2000. pp 511-538.

Gasińska A, Biesaga B. The two aspects of tumour hypoxia. Nowotwory J Oncol. 2010;60(4):332. doi:10.5603/njo.52151

Afford S, Randhawa S. Apoptosis. Mol Pathol. 2000;53(2):55-63. doi:10.1136/mp.53.2.55

Kopiński P, Chorostowska-Wynimko J, Dyczek A, Giżycka A. Apoptosis of alveolar lymphocytes. Part 1: pathways of lymphocyte apoptosis. Adv Respir Med. 2014;82(2):170-182. doi:10.5603/PiAP.2014.0023

Żuryń A, Grzanka A, Stępień A, Grzanka D, Dębski R, Smoliński D. Expression of cyclin A in human leukemia cell line HL-60 following treatment with doxorubicin and etoposide: the potential involvement of cyclin A in apoptosis. Oncol Rep. 2007;17:1013-1019. doi:10.3892/or.17.5.101

Stenzel A, Żuryń A, Grzanka AA, Grzanka A. Cyclins as a markers of cancer diseases. Nowotwory J Oncol. 2012;62(2):115-122. doi:10.5603/njo.19142.

Suzuki F, Hashimoto K, Kikuchi H, et al. Induction of tumor-specific cytotoxicity and apoptosis by doxorubicin. Anticancer Res. 2005;25:887-894.

Chatterjee K, Zhang J, Honbo N, Karliner JS. Doxorubicin cardiomyopathy. Cardiology. 2010;115(2):155-162. doi:10.1159/000265166

Sheibani M, Azizi Y, Shayan M, et al. Doxorubicin-induced cardiotoxicity: An overview on pre-clinical therapeutic approaches. Cardiovasc Toxicol. 2022;22:292-310. doi:10.1007/s12012-022-09721-1

Pai VB, Nahata MC. Cardiotoxicity of chemotherapeutic agents: incidence, treatment and prevention. Drug Saf. 2000;22(4):263-302. doi:10.2165/00002018-200022040-00002

Christidi E, Brunham LR. Regulated cell death pathways in doxorubicin-induced cardiotoxicity. Cell Death Dis. 2021;12:339. doi:10.1038/s41419-021-03614-x

Kong CY, Guo Z, Song P, Zhang X, Yuan YP, Teng T, Yan L, Tang QZ. Underlying the mechanisms of doxorubicin-induced acute cardiotoxicity: oxidative stress and cell death. Int J Biol Sci. 2022;18(2):760-770. doi:10.7150/ijbs.65258

Oktem O, Oktay K. Quantitative assessment of the impact of chemotherapy on ovarian follicle reserve and stromal function. Cancer. 2007;110:2222-2229. doi:10.1002/cncr.23071

Ben-Aharon I, Bar-Joseph H, Tzarfaty G, et al. Doxorubicin-induced ovarian toxicity. Reprod Biol Endocrinol. 2010;8:20. doi:10.1186/1477-7827-8-20

Kostrzewa-Nowak, D., Paine, M., Wolf, C. et al.The role of bioreductive activation of doxorubicin in cytotoxic activity against leukaemia HL60-sensitive cell line and its multidrug-resistant sublines. Br J Cancer, 2005;93:89-97.doi:10.1038/sj.bjc.6602639

Al-Abbasa NS, Shaer NA. Combination of coumarin and doxorubicin induces drug-resistant acute myeloid leukemia cell death. Heliyon. 2021;7:e06255. doi:10.1016/j.heliyon.2021.e06255

Chen J, Wei H, Cheng J, et al. Characteristics of doxorubicin-selected multidrug-resistant human leukemia HL-60 cells with tolerance to arsenic trioxide and contribution of leukemia stem cells. Oncol Lett. 2018;15(2):1255-1262. doi:10.3892/ol.2017.7353

Downloads

Published

2025-12-30

How to Cite

Rzeszutek, D., & Kuna, E. (2025). Doxorubicin-induced cell cycle arrest and apoptosis in HL-60 leukemia cells – a narrative review. European Journal of Clinical and Experimental Medicine, 23(4), 1081–1087. https://doi.org/10.15584/ejcem.2025.4.30

Issue

Section

REVIEW PAPERS