Novel Selective Anticancer Effect of Epididymis-Derived Extracellular Vesicles Against HCC38 and MCF-7 Breast Cancer Cell Lines

Sep 22, 2026

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Prevalent cancers include breast, lung and bronchus, prostate, and colorectal cancers, while epididymis cancer is rare. This study proposes that epididymis tissue contains inherent anticancer components, especially small extracellular vesicles (EVs) with antineoplastic properties. Small EVs (30–200 nm) can transfer lipids, proteins, DNA, and RNA to target cells, driving processes such as growth, division, or apoptosis. Here, epididymis-derived small EVs were isolated and tested on HCC38 and MCF-7 breast cancer cell lines, plus a normal fibroblast line. The findings show selective action on cancer cells, including increased apoptosis, cell-cycle arrest, and elevated pro-apoptotic p53 expression, with significant uptake correlating with biological response, supporting therapeutic potential for Ep-EVs.

LanguageEnglish

CategoryResearch & Report

FormatPDF

Pages24

Reading Time1 h 0 min

AccessFree to download

Abstract

Keywords

1. Introduction

Breast cancer treatment and therapeutic resistance

Extracellular vesicles as anticancer agents

Article Novel Selective Anticancer Effect of Epididymis-Derived Extracellular Vesicles Against HCC38 and MCF-7 Breast Cancer Cell Lines Razi Zoabi 1,2,†, Zenab Ali Saleh 1,2,†, Elias Issaq 3, Etedal Morad 4, Reem Miari 5, Hanan Taha 1, Ahmad Kadriya 1,2, Abraham O. Samson 2 and Mizied Falah 1,2, * Academic Editor: Su-Yun Lyu Received: 12 March 2026 Revised: 13 April 2026 Accepted: 16 April 2026 Published: 27 April 2026 Copyright: © 2026 by the authors. Licensee MDPI, Basel, Switzerland. This article is an open access article distributed under the terms and conditions of the Creative Commons Attribution (CC BY) license. 1 Medical Research Institute, The Holy Family Hospital, Nazareth 16100, Israel 2 Azrieli Faculty of Medicine, Bar-Ilan University, Safed 1311502, Israel 3 Department of Urology, The Holy Family Hospital, Nazareth 16100, Israel 4 Department of Pathology, The Holy Family Hospital, Nazareth 16100, Israel; [etedal.m@hfhosp.org](etedal.m@hfhosp.org) 5 Exocure Therapeutics, Industrial Park, Sakhnin 308100, Israel * [Correspondence: mizied.falah@gmail.com](Correspondence: mizied.falah@gmail.com); Tel.: +972-74-723-1736 † These authors contributed equally to this work. Abstract Prevalent cancers primarily include breast, lung and bronchus, prostate, and colorectal cancers. In contrast, cancer of the epididymis is very rare, and we propose that this tissue could carry inherent anticancer components, in particular, small extracellular vesicles (EVs) with antineoplastic properties. All cell types release extracellular vesicles (EVs) into their intercellular space, which act in the crosstalk required to achieve homeostasis. Among these, small EVs, which are membrane-bound vesicles with an average diameter of 30–200 nm, can transfer cell-specific cargo, such as lipids, proteins, DNA and RNA, which can be selectively received by neighboring or distant cells, and trigger specific cell processes, such as growth, division, or apoptosis. Here, we isolated small EVs from epididymis tissue, and examined their effect on morphology, viability, apoptosis, cell cycle phases, and certain gene and protein expression levels, particularly of the pro-apoptotic p53 protein, in HCC38 and MCF-7 breast cancer cell lines, as well as in a normal fibroblast cell line. The various analyses demonstrated effects on breast cancer cells but not on normal cells. Specifically, epididymis-derived EVs (Ep-EVs) selectively induced apoptosis and cell cycle arrest in cancer cells, while normal cells were unaffected. Moreover, the relative uptake of Ep-EVs in HCC38 and MCF-7 breast cancer cells was significant, indicating a direct association between vesicle internalization and the biological response. Taken together, these findings demonstrate a solid experimental foundation supporting the therapeutic potential of Ep-EVs in breast cancer, with promising implications for their development asa broader anticancer platform. Keywords: extracellular vesicles; epididymis-derived EVs; breast cancer; apoptosis; p53 1. Introduction Breast cancer is one of the most common malignancies worldwide and remains a leading cause of cancer-related mortality among women [1–3] . Despite significant advancesin diagnosis and treatment strategies, some types of breast cancer remain difficult to cure. Historically, breast tumors have been treated with different strategies. Surgical management therapy has evolved from radical mastectomy to modified versions thereof, and more recently to breast-conserving surgery guided by locoregional approaches [4,5] . In addition, systemic chemotherapy is used to treat tumors with a poor prognosis [6] . Neoadjuvant chemotherapy is administered before surgery to reduce tumor size, improve surgical outcomes, and limit metastatic spread [7] . In contrast, adjuvant chemotherapy and radiotherapy are administered after surgery, to eliminate residual malignant cells and thereby reduce the risk of cancer recurrence [8

FAQs

Why focus on epididymis-derived extracellular vesicles for cancer therapy?

Epididymis tissue is proposed to contain intrinsic antineoplastic components, particularly small extracellular vesicles that can transfer bioactive cargo and trigger apoptosis pathways in cancer cells.

How were the epididymis-derived EVs evaluated in this study?

Small EVs were isolated from epididymis tissue and assessed for their effects on cancer-cell morphology, viability, apoptosis, cell-cycle phases, and specific gene/protein expression, especially p53.

Did the epididymis-derived EVs affect cancer cells and normal cells differently?

Yes. The analyses demonstrated effects on breast cancer cells but not on the normal fibroblast line; Ep-EVs selectively induced apoptosis and cell-cycle arrest in cancer cells, while normal cells remained unaffected.

Sep 22, 2026

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