Pharmacological Properties and the Impact of Caffeic Acid-Entrapped Liposomes on Triple-Negative Breast Cancer Cell Lines Exposed to Doxorubicin

Dejeu, Ioana-Lavinia; Olteanu, Diana; Clichici, Simona; Baldea, Ioana; Soritău, Olga; Frenț, Olimpia-Daniela; Marian, Nicole Alina; Mureșan, Mariana Eugenia; Svera, Paula; Marian, Eleonora; Dejeu, George Emanuiel; Vicaș, Laura Grațiela; Filip, Gabriela Adriana

doi:10.3390/antiox15040424

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Open AccessArticle

Pharmacological Properties and the Impact of Caffeic Acid-Entrapped Liposomes on Triple-Negative Breast Cancer Cell Lines Exposed to Doxorubicin

by

Ioana-Lavinia Dejeu

^1,†,

Diana Olteanu

^2,†,

Simona Clichici

²

,

Ioana Baldea

²

,

Olga Soritău

³

,

Olimpia-Daniela Frenț

¹,

Nicole Alina Marian

⁴,

Mariana Eugenia Mureșan

⁴,

Paula Svera

⁵,

Eleonora Marian

¹

,

George Emanuiel Dejeu

⁶,

Laura Grațiela Vicaș

^1,*

and

Gabriela Adriana Filip

⁷

¹

Department of Pharmacy, Faculty of Medicine and Pharmacy, University of Oradea, No. 29 Nicolae Jiga Street, 410028 Oradea, Romania

²

Department of Physiology, ‘‘Iuliu Hațieganu” University of Medicine and Pharmacy, 1-3 Clinicilor Street, 400006 Cluj-Napoca, Romania

³

Radiobiology and Tumor Biology Laboratory, Oncological Institute “Prof. Dr. I. Chiricuță”, 34–36 Republicii Street, 400015 Cluj-Napoca, Romania

⁴

Doctoral School of Biomedical Sciences, University of Oradea, No. 1 University Street, 410087 Oradea, Romania

⁵

National Institute for Research and Development in Electrochemistry and Condensed Matter, 144th Dr. A.P. Podeanu Street, 300569 Timisoara, Romania

⁶

Department of Surgical Disciplines, Faculty of Medicine and Pharmacy, University of Oradea, 10 Piata 1 Decembrie Street, 410073 Oradea, Romania

⁷

Department of Anatomy and Embryology, “Iuliu Hatieganu” University of Medicine and Pharmacy, no 8 Victor Babeș Street, 400012 Cluj-Napoca, Romania

^*

Author to whom correspondence should be addressed.

^†

These authors contributed equally to this work.

Antioxidants 2026, 15(4), 424; https://doi.org/10.3390/antiox15040424

Submission received: 5 February 2026 / Revised: 24 March 2026 / Accepted: 26 March 2026 / Published: 27 March 2026

(This article belongs to the Section Health Outcomes of Antioxidants and Oxidative Stress)

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Abstract

Background: Caffeic acid (CA), with antioxidant and immunomodulatory properties, was formulated in liposomes to increase its efficacy. The study targets triple-negative breast cancer (TNBC), characterized by the absence of ER, PR, and HER2 receptors. Methods: For CA-loaded liposomes, the pharmacological effects on TNBC cell lines, parental Hs578T (HS) and Doxorubicin-resistant Hs578T (HSD) cells were evaluated by determining the cell growth inhibition ratio measured by the (3-[4,5-dimethylthiazol-2-yl]-2,5 diphenyl tetrazolium bromide) assay, oxidative stress, apoptosis rate, membrane damage and transcription factor expressions, and DNA damage, with or without exposure to Doxorubicin (Dox). The Results: demonstrated that CA-loaded liposomes were stable and had high entrapment capacity. They exerted apoptotic effects on both cells, comparable to Doxorubicin, and increased cell membrane damage. The liposomes increased STAT3 expression in HS cells, while they reduced NRF2 and STAT3 in HSD cells, suggesting beneficial effects on Dox-resistant breast tumor cells. In HS cells exposed to Dox, CA treatment improved the number of viable tumor cells and decreased the rate of apoptosis, while in HSD cells it enhanced apoptosis as a mechanism of cell death and decreased pro-survival molecules, STAT3 expression in parallel with reduced NRF2 activation. Conclusions: The results indicated that CA encapsulated in liposomes was able to interfere with some survival mechanisms of triple-negative cells and could inhibit their proliferation.

Keywords: caffeic acid; liposomes; doxorubicin; breast cancer cell; oxidative stress

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MDPI and ACS Style

Dejeu, I.-L.; Olteanu, D.; Clichici, S.; Baldea, I.; Soritău, O.; Frenț, O.-D.; Marian, N.A.; Mureșan, M.E.; Svera, P.; Marian, E.; et al. Pharmacological Properties and the Impact of Caffeic Acid-Entrapped Liposomes on Triple-Negative Breast Cancer Cell Lines Exposed to Doxorubicin. Antioxidants 2026, 15, 424. https://doi.org/10.3390/antiox15040424

AMA Style

Dejeu I-L, Olteanu D, Clichici S, Baldea I, Soritău O, Frenț O-D, Marian NA, Mureșan ME, Svera P, Marian E, et al. Pharmacological Properties and the Impact of Caffeic Acid-Entrapped Liposomes on Triple-Negative Breast Cancer Cell Lines Exposed to Doxorubicin. Antioxidants. 2026; 15(4):424. https://doi.org/10.3390/antiox15040424

Chicago/Turabian Style

Dejeu, Ioana-Lavinia, Diana Olteanu, Simona Clichici, Ioana Baldea, Olga Soritău, Olimpia-Daniela Frenț, Nicole Alina Marian, Mariana Eugenia Mureșan, Paula Svera, Eleonora Marian, and et al. 2026. "Pharmacological Properties and the Impact of Caffeic Acid-Entrapped Liposomes on Triple-Negative Breast Cancer Cell Lines Exposed to Doxorubicin" Antioxidants 15, no. 4: 424. https://doi.org/10.3390/antiox15040424

APA Style

Dejeu, I.-L., Olteanu, D., Clichici, S., Baldea, I., Soritău, O., Frenț, O.-D., Marian, N. A., Mureșan, M. E., Svera, P., Marian, E., Dejeu, G. E., Vicaș, L. G., & Filip, G. A. (2026). Pharmacological Properties and the Impact of Caffeic Acid-Entrapped Liposomes on Triple-Negative Breast Cancer Cell Lines Exposed to Doxorubicin. Antioxidants, 15(4), 424. https://doi.org/10.3390/antiox15040424

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Pharmacological Properties and the Impact of Caffeic Acid-Entrapped Liposomes on Triple-Negative Breast Cancer Cell Lines Exposed to Doxorubicin

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