Open Access

ARTICLE

Interplay of Interleukin-1β and Curcumin on VEGF Expression in Breast Cancer Cells

Norbert Nass^1,2,*, Atanas Ignatov³, Thomas Kalinski¹

1 Institute of Pathology, University Hospital Brandenburg/Havel, Brandenburg Medical School Theodor Fontane (MHB), Brandenburg an der Havel, 14770, Germany
2 Institute of Pathology, Otto von Guericke University Magdeburg, Magdeburg, 39120, Germany
3 Department of Obstetrics and Gynecology, Otto von Guericke University Magdeburg, Magdeburg, 39108, Germany

* Corresponding Author: Norbert Nass. Email:

Oncology Research 2026, 34(3), 13 https://doi.org/10.32604/or.2025.072793

Received 03 September 2025; Accepted 09 December 2025; Issue published 24 February 2026

Abstract

Objectives: Vascular endothelial growth factor (VEGF) regulates tumor vascularization in response to hypoxia and inflammatory signals. The polyphenol curcumin is supposed to interfere with inflammation-induced VEGF secretion and might therefore support anti-VEGF-based treatments. We aimed to investigate the interaction between curcumin and the inflammatory cytokine Interleukin-1β (IL-1β) for VEGF secretion in breast cancer cell lines representing major breast cancer subtypes. Methods: VEGF in cell cultures was detected by Western blot and enzyme-linked immunosorbent assay (ELISA). Kinase phosphorylation was investigated by Western blotting. Gene expressions were analyzed by correlation tests. VEGF was evaluated in a retrospective breast cancer cohort by immunohistochemistry. Survival analysis was performed by the Kaplan-Meier algorithm. Results: VEGF secretion and kinase signaling in response to IL-1β and curcumin varied significantly for the cell lines MCF-7 (Luminal A), SK-BR-3 (HER2/neu+), MDA-MB-231, and UACC-3199 (triple negative breast cancer). All cell lines increased VEGF secretion under hypoxia, but IL-1β increased VEGF secretion only in MCF-7 cells. Curcumin inhibited VEGF secretion in MDA-MB-231, but increased it in MCF-7 and UACC-3199 cells. Curcumin induced phosphorylation of extracellular signal-regulated kinase (ERK) and p38-mitogen-activated protein kinase (p38-MAPK). However, inhibitor experiments demonstrated that ERK was more important for VEGF secretion. In gene expression data from the METABRIC study, no clear correlation of hypoxia-induced factor (HIF1A), IL-1β, and VEGF mRNA expression was observed; however, a suggested crosstalk of hypoxia and inflammatory pathways was observed. Conclusion: These dissimilar responses of breast cancer cell lines suggest that therapy efficiency with anti-VEGF, anti-IL-1β, or curcumin will also vary within breast cancers.

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Supplementary Material

Supplementary Material File

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