Ukr.Biochem.J. 2026; Volume 98, Issue 3, May-Jun, pp. 101-111
doi: https://doi.org/10.15407/ubj98.03.101
Curcumin boosts doxorubicin cytotoxicity in breast cancer cells
, , , ,
, ,
1Department of Molecular Immunology, Palladin Institute of Biochemistry,
National Academy of Sciences of Ukraine, Kyiv;
2Department of Technologies of Medical Diagnostics and Treatment,
ESC “Institute of Biology and Medicine”, Taras Shevchenko National University of Kyiv, Ukraine;
3Department of General and Soil Microbiology, D.K. Zabolontny Institute of Microbiology
and Virology, National Academy of Sciences of Ukraine, Kyiv;
4Department of Microbiology and Immunology,
ESC “Institute of Biology and Medicine”, Taras Shevchenko National University of Kyiv, Ukraine
*e-mail: andriisiromolot@knu.ua
Received: 04 February 2026; Revised: 13 April 2026;
Accepted: 29 May 2026; Available on-line: 18 June 2026
Background. Breast cancer remains the leading cause of cancer mortality in women due to the resistance to chemotherapy and severe side effects of doxorubicin (Doxo). One of the approaches to overcome this problem is to search for phytocompounds that can enhance the efficacy of chemotherapy and prevent the development of side effects. Objective. This work aimed to investigate in vitro whether the polyphenol curcumin (Cur) from turmeric (Curcuma longa) in combination with the commercial drug Doxo-HCl can enhance the cytotoxic effect of Doxo on breast cancer cell lines MDA-MB-231 and MCF-7 and to exhibit chemoprotective activity against normal HEK-293 cells. Methods. Cell viability was assessed with MTT assay, apoptosis induction by flow cytometry with Annexin V–eGFP and PI, reactive oxygen species (ROS) generation by the DCFH-DA probe. The combination index (CI) calculation method and CompuSyn, Biosoft software were used to determine the synergism or antagonism of the components. Results. The study revealed dose-dependent cytotoxicity, increased ROS formation, and increased morphological aberrations in cells when using the combination of Cur with Doxo-HCl compared to Doxo-HCl. Cur acted as a chemosensitizer, which synergistically enhanced the antitumor activity of Doxo-HCl while simultaneously reducing its cytotoxic effects in normal cells by reducing ROS production. Conclusions. The use of Cur in combination with Doxo-HCl will likely reduce the effective therapeutic dose of Doxo and increase the effectiveness of breast cancer chemotherapy.
Keywords: apoptosis, breast cancer cell lines, cell viability, chemosensitizer, combination index, combined treatment, curcumin, doxorubicin, oxidative stress
References:
- Bray F, Laversanne M, Sung H, Ferlay J, Siegel RL, Soerjomataram I, Jemal A. Global cancer statistics 2022: GLOBOCAN estimates of incidence and mortality worldwide for 36 cancers in 185 countries. CA Cancer J Clin. 2024;74(3):229-263. PubMed, CrossRef
- Burguin A, Diorio C, Durocher F. Breast Cancer Treatments: Updates and New Challenges. J Pers Med. 2021;11(8):808. PubMed, PubMedCentral, CrossRef
- Bergin ART, Loi S. Triple-negative breast cancer: recent treatment advances. F1000Res. 2019;8(F1000 Faculty Rev):1342. PubMed, PubMedCentral, CrossRef
- Kciuk M, Gielecińska A, Mujwar S, Kołat D, Kałuzińska-Kołat Ż, Celik I, Kontek R. Doxorubicin-An Agent with Multiple Mechanisms of Anticancer Activity. Cells. 2023;12(4):659. PubMed, PubMedCentral, CrossRef
- Hulst MB, Zhang L, van der Heul HU, Du C, Elsayed SS, Koroleva A, Grocholski T, Wander DPA, Metsä-Ketelä M, Neefjes JJC, van Wezel GP. Metabolic engineering of Streptomyces peucetius for biosynthesis of N,N-dimethylated anthracyclines. Front Bioeng Biotechnol. 2024;12:1363803. PubMed, PubMedCentral, CrossRef
- Carvalho C, Santos RX, Cardoso S, Correia S, Oliveira PJ, Santos MS, Moreira PI. Doxorubicin: the good, the bad and the ugly effect. Curr Med Chem. 2009;16(25):3267-3285. PubMed, CrossRef
- Menna P, Recalcati S, Cairo G, Minotti G. An introduction to the metabolic determinants of anthracycline cardiotoxicity. Cardiovasc Toxicol. 2007;7(2):80-85. PubMed, CrossRef
- Xia W, King MW. Advances in Targeted Delivery of Doxorubicin for Cancer Chemotherapy. Bioengineering (Basel). 2025;12(4):430. PubMed, PubMedCentral, CrossRef
- Guestini F, McNamara KM, Sasano H. The Use of Chemosensitizers to Enhance the Response to Conventional Therapy in Triple-Negative Breast Cancer Patients. Breast Cancer Manag. 2017;6(4):127-131. CrossRef
- Kaur K, Al-Khazaleh AK, Bhuyan DJ, Li F, Li CG. A Review of Recent Curcumin Analogues and Their Antioxidant, Anti-Inflammatory, and Anticancer Activities. Antioxidants (Basel). 2024;13(9):1092. PubMed, PubMedCentral, CrossRef
- Lasoff DR, Cantrell FL, Ly BT. Death associated with intravenous turmeric (Curcumin) preparation. Clin Toxicol (Phila). 2018;56(5):384-385. PubMed, CrossRef
- Calaf GM, Ponce-Cusi R, Carrión F. Curcumin and paclitaxel induce cell death in breast cancer cell lines. Oncol Rep. 2018;40(4):2381-2388. PubMed, CrossRef
- Ashrafizadeh M, Zarrabi A, Hashemi F, Zabolian A, Saleki H, Bagherian M, Azami N, Bejandi AK, Hushmandi K, Ang HL, Makvandi P, Khan H, Kumar AP. Polychemotherapy with Curcumin and Doxorubicin via Biological Nanoplatforms: Enhancing Antitumor Activity. Pharmaceutics. 2020;12(11):1084. PubMed, PubMedCentral, CrossRef
- Zoi V, Galani V, Lianos GD, Voulgaris S, Kyritsis AP, Alexiou GA. The Role of Curcumin in Cancer Treatment. Biomedicines. 2021;9(9):1086. PubMed, PubMedCentral, CrossRef
- Fatima F, Chourasiya NK, Mishra M, Kori S, Pathak S, Das R, Kashaw V, Iyer AK, Kashaw SK. Curcumin and its Derivatives Targeting Multiple Signaling Pathways to Elicit Anticancer Activity: A Comprehensive Perspective. Curr Med Chem. 2024;31(24):3668-3714. PubMed, CrossRef
- Akter K, Gul K, Mumtaz S. Revisiting Curcumin in Cancer Therapy: Recent Insights into Molecular Mechanisms, Nanoformulations, and Synergistic Combinations. Curr Issues Mol Biol. 2025;47(9):716. PubMed, PubMedCentral, CrossRef
- Wang B, Li W, Hong W, Wang J, Tao L, Shen S. Chemoresistance mitigation of dual drug-loaded nanoparticles with doxorubicin and curcumin. Cytotechnology. 2025;77(6):196. PubMed, PubMedCentral, CrossRef
- Siromolot AA, Krynina OI, Kolybo DV, Komisarenko SV. Antiproliferative and apoptotic effects of anti-human HB-EGF neutralizing polyclonal antibodies in vitro. Exp Oncol. 2020;42(1):25-30. PubMed, CrossRef
- Siromolot A, Zhukova D, Romaniuk S, Kolybo D, Komisarenko S. Multiple strategies for HB-EGF inhibition: interference with receptor binding, ectodomain shedding and matricrine signaling. Biochimie. 2026;244:136-146. PubMed, CrossRef
- Chou TC. Theoretical basis, experimental design, and computerized simulation of synergism and antagonism in drug combination studies. Pharmacol Rev. 2006;58(3):621-681. PubMed, CrossRef
- Ma J, Zhang Y, Du J, Chen J, Sun J, Ma X, Zeng J, Efferth T. High-fat Diet-associated Digestive Cancers: Mechanisms, Natural Product-based Therapies, and Drug Development. Phytomedicine. 2026;150:157574. PubMed, CrossRef
- Vladu AF, Ficai D, Ene AG, Ficai A. Combination Therapy Using Polyphenols: An Efficient Way to Improve Antitumoral Activity and Reduce Resistance. Int J Mol Sci. 2022;23(18):10244. PubMed, PubMedCentral, CrossRef
- Zhukova D, Katashynska D, Siromolot A, Romaniuk S, Kolybo D, Komisarenko S. Nontoxic diphtheria toxin derivates CRM197 and B-fragment can serve as the means for targeted curcumin delivery into sensitive cancers cells. J Drug Deliv Sci Technol. 2024;96:105673. CrossRef
- Alizadeh SR, Savadkouhi N, Ebrahimzadeh MA. Drug design strategies that aim to improve the low solubility and poor bioavailability conundrum in quercetin derivatives. Expert Opin Drug Discov. 2023;18(10):1117-1132. PubMed, CrossRef
- Pillai U J, Singh P, Maan M, Nidagodu Jayakumar M, Donakonda S, Iype E, Dutta M. Drug repurposing identifies novel Wee1 kinase inhibitors for triple negative breast cancer therapeutics. Eur J Med Chem. 2026;302(Pt 3):118340. PubMed, CrossRef
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