# Unraveling the therapeutic potential of Elaeagnus angustifolia extract on triple-negative breast cancer (TNBC): An investigation using zebrafish model

**Authors:** Haya Abuhijleh, Zain Zakria, Hiba Bawadi, Ayat Hammad, Ala-Eddin Al Moustafa, Abdullah Shaito, Maha Al-Asmakh

PMC · DOI: 10.1371/journal.pone.0344247 · 2026-03-06

## TL;DR

This study explores the potential of Elaeagnus angustifolia extract to treat triple-negative breast cancer using a zebrafish model, finding it safe and effective at reducing tumor cell growth.

## Contribution

The study is the first to investigate the anti-TNBC effects of Elaeagnus angustifolia extract in a zebrafish xenograft model.

## Key findings

- Elaeagnus angustifolia extract showed a dose-dependent reduction in TNBC cell fluorescence in zebrafish xenografts.
- Safe, non-toxic concentrations of the extract were identified (0.5 mg/mL and 0.75 mg/mL).
- The extract suppressed tumor cell proliferation and survival in the zebrafish model.

## Abstract

Breast cancer is a widespread and aggressive disease, with 2.3 million new cases globally in 2022. Metastasis, the spread of cancer cells to distant organs, remains a leading cause of breast cancer-related mortality. Current treatment options, particularly traditional chemotherapeutic drugs, are often associated with severe side effects, emphasizing the urgent need for safer and more effective therapeutic alternatives. Triple-negative breast cancer (TNBC) represents one of the most aggressive breast cancer subtypes, characterized by the absence of estrogen receptors (ER), receptors (PR), and HER2 expression. The human TNBC cell line MDA-MB-231, was selected in this study due to its aggressive, metastatic phenotype and its well-established use in zebrafish xenograft models. This makes it a highly relevant platform for preliminary in vivo evaluation of novel plant-derived compounds, particularly those targeting hard-to-treat breast cancer subtypes such as TNBC. Elaeagnus angustifolia (EA), commonly known as Russian olive, has attracted interest for its antimicrobial, anti-inflammatory, and antioxidant properties. However, its potential anticancer activity, especially against TNBC, remains relatively unexplored. This research investigated the efficacy of EA extract against MDA-MB-231 TNBC cells using a wild-type AB zebrafish model. A key objective was to evaluate the toxicological profile of EA across multiple physiological parameters in zebrafish, including developmental, cardiovascular, neuromuscular, and hepatic functions. The study identified safe, non-toxic concentrations of EA extract (0.5 mg/mL and 0.75 mg/mL). Moreover, treatment with EA in zebrafish xenografts led to a dose-dependent reduction in fluorescence intensity of injected TNBC cells, suggesting suppression of tumor cell proliferation and survival.. These findings suggest that EA warrant further investigation as a potential anticancer agent for TNBC. The observed safety profile and preliminary anti-tumor effects in zebrafish provide a foundation for future mechanistic and mammalian studies.

## Linked entities

- **Diseases:** triple-negative breast cancer (MONDO:0005494), breast cancer (MONDO:0004989)
- **Species:** Danio rerio (taxon 7955), Mus musculus (taxon 10090)

## Full-text entities

- **Genes:** TP53 (tumor protein p53) [NCBI Gene 7157] {aka BCC7, BMFS5, LFS1, P53, TRP53}, casp3a (caspase 3, apoptosis-related cysteine peptidase a) [NCBI Gene 140621] {aka casp3, zgc:100890}, cdkn1ba (cyclin dependent kinase inhibitor 1Ba) [NCBI Gene 402862] {aka cdkn1bl}, ERBB2 (erb-b2 receptor tyrosine kinase 2) [NCBI Gene 2064] {aka CD340, HER-2, HER-2/neu, HER2, MLN 19, MLN-19}, COL11A2 (collagen type XI alpha 2 chain) [NCBI Gene 1302] {aka DFNA13, DFNB53, FBCG2, HKE5, OSMEDA, OSMEDB}, fscn1a (fascin actin-bundling protein 1a) [NCBI Gene 558271] {aka fscn1, sb:cb589, zgc:153632}, CLDN3 (claudin 3) [NCBI Gene 1365] {aka C7orf1, CPE-R2, CPETR2, HRVP1, RVP1}, PGR (progesterone receptor) [NCBI Gene 5241] {aka NR3C3, PR}, casp9 (caspase 9, apoptosis-related cysteine peptidase) [NCBI Gene 492763] {aka im:7136887, zgc:101776}, CD44 (CD44 molecule (IN blood group)) [NCBI Gene 960] {aka CDW44, CSPG8, ECM-III, ECMR-III, H-CAM, HCELL}, vim (vimentin) [NCBI Gene 140599] {aka cb28}, EREG (epiregulin) [NCBI Gene 2069] {aka EPR, ER, Ep}, CLDN4 (claudin 4) [NCBI Gene 1364] {aka CPE-R, CPER, CPETR, CPETR1, WBSCR8, hCPE-R}, cdkn1a (cyclin dependent kinase inhibitor 1A) [NCBI Gene 100151416] {aka cip1, p21, si:ch1073-48m5.2, waf1}, ESR1 (estrogen receptor 1) [NCBI Gene 2099] {aka ER, ESR, ESRA, ESTRR, Era, NR3A1}, CDH1 (cadherin 1) [NCBI Gene 999] {aka Arc-1, BCDS1, CD324, CDHE, ECAD, LCAM}, MAPK3 (mitogen-activated protein kinase 3) [NCBI Gene 5595] {aka ERK-1, ERK1, ERT2, HS44KDAP, HUMKER1A, P44ERK1}, BRCA1 (BRCA1 DNA repair associated) [NCBI Gene 672] {aka BRCAI, BRCC1, BROVCA1, FANCS, IRIS, PNCA4}, cdh1 (cadherin 1, type 1, E-cadherin (epithelial)) [NCBI Gene 114424] {aka E-cadherin}, CD274 (CD274 molecule) [NCBI Gene 29126] {aka ADMIO5, B7-H, B7H1, PD-L1, PDCD1L1, PDCD1LG1}, tp53 (tumor protein p53) [NCBI Gene 30590] {aka brp53, drp53, etID22686.5, fb40d06, p53, wu:fb40d06}, MAPK1 (mitogen-activated protein kinase 1) [NCBI Gene 5594] {aka ERK, ERK-2, ERK2, ERT1, MAPK2, NS13}, MAPK8 (mitogen-activated protein kinase 8) [NCBI Gene 5599] {aka JNK, JNK-46, JNK1, JNK1A2, JNK21B1/2, PRKM8}
- **Diseases:** yolk sac edema (MESH:D018240), Neuromuscular toxicity (MESH:D020511), Cardiotoxicity (MESH:D066126), teratogenicity (MESH:C535542), pleural effusion (MESH:D010996), hepatic steatosis (MESH:D005234), adenocarcinoma (MESH:D000230), Tumors (MESH:D009369), neurotoxicity (MESH:D020258), reduction in locomotor activity (MESH:D001523), edema (MESH:D004487), head and neck cancer (MESH:D006258), inflammatory (MESH:D007249), developmental abnormalities (MESH:D006130), hepatic lipid (MESH:D011017), neuromuscular impairment (MESH:D009468), malformations (MESH:C564254), looping defects (MESH:D001765), overdose (MESH:D062787), Breast cancer (MESH:D001943), TNBC (MESH:D064726), positive (MESH:D000377), organ toxicity (MESH:D019965), developmental impairments (MESH:D007805), Developmental toxicity (MESH:D064420), Metastasis (MESH:D009362), hormone receptor (MESH:D046150), Death (MESH:D003643)
- **Chemicals:** isopropanol (MESH:D019840), ethanol (MESH:D000431), methylcellulose (MESH:D008747), water (MESH:D014867), Zinc Oxide (MESH:D015034), atezolizumab (MESH:C000594389), ORO (MESH:C011049), tamoxifen (MESH:D013629), streptomycin (MESH:D013307), Herceptin (MESH:D000068878), PBS (MESH:D007854), Tween (MESH:D011136), MS-222 (MESH:C003636), Flavonoids (MESH:D005419), talazoparib (MESH:C586365), CO2 (MESH:D002245), sacituzumab govitecan (MESH:C000608132), olaparib (MESH:C531550), agarose (MESH:D012685), lipid (MESH:D008055), paraformaldehyde (MESH:C003043), pembrolizumab (MESH:C582435), aluminum (MESH:D000535), CM-DiI Red Fluorescent Protein (-), penicillin (MESH:D010406)
- **Species:** Enterovirus A (no rank) [taxon 138948], Olea europaea (common olive, species) [taxon 4146], Elaeagnus angustifolia (oleaster, species) [taxon 36777], Homo sapiens (human, species) [taxon 9606], Danio rerio (leopard danio, species) [taxon 7955]
- **Mutations:** E3, E3M
- **Cell lines:** MDA-MB-231 — Homo sapiens (Human), Breast adenocarcinoma, Cancer cell line (CVCL_0062)

## Figures

7 figures with captions in the complete paper: https://tomesphere.com/paper/PMC12965599/full.md

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Source: https://tomesphere.com/paper/PMC12965599