{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,4,29]],"date-time":"2026-04-29T03:10:16Z","timestamp":1777432216076,"version":"3.51.4"},"reference-count":66,"publisher":"MDPI AG","issue":"9","license":[{"start":{"date-parts":[[2026,4,27]],"date-time":"2026-04-27T00:00:00Z","timestamp":1777248000000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"funder":[{"name":"Exocure Therapeutics Company"}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":["IJMS"],"abstract":"<jats:p>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\u2013200 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 as a broader anticancer platform.<\/jats:p>","DOI":"10.3390\/ijms27093870","type":"journal-article","created":{"date-parts":[[2026,4,28]],"date-time":"2026-04-28T11:33:37Z","timestamp":1777376017000},"page":"3870","update-policy":"https:\/\/doi.org\/10.3390\/mdpi_crossmark_policy","source":"Crossref","is-referenced-by-count":0,"title":["Novel Selective Anticancer Effect of Epididymis-Derived Extracellular Vesicles Against HCC38 and MCF-7 Breast Cancer Cell Lines"],"prefix":"10.3390","volume":"27","author":[{"ORCID":"https:\/\/orcid.org\/0009-0004-1414-7684","authenticated-orcid":false,"given":"Razi","family":"Zoabi","sequence":"first","affiliation":[{"name":"Medical Research Institute, The Holy Family Hospital, Nazareth 16100, Israel"},{"name":"Azrieli Faculty of Medicine, Bar-Ilan University, Safed 1311502, Israel"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"ORCID":"https:\/\/orcid.org\/0009-0008-9525-1633","authenticated-orcid":false,"given":"Zenab","family":"Ali Saleh","sequence":"additional","affiliation":[{"name":"Medical Research Institute, The Holy Family Hospital, Nazareth 16100, Israel"},{"name":"Azrieli Faculty of Medicine, Bar-Ilan University, Safed 1311502, Israel"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Elias","family":"Issaq","sequence":"additional","affiliation":[{"name":"Department of Urology, The Holy Family Hospital, Nazareth 16100, Israel"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Etedal","family":"Morad","sequence":"additional","affiliation":[{"name":"Department of Pathology, The Holy Family Hospital, Nazareth 16100, Israel"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Reem","family":"Miari","sequence":"additional","affiliation":[{"name":"Exocure Therapeutics, Industrial Park, Sakhnin 308100, Israel"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Hanan","family":"Taha","sequence":"additional","affiliation":[{"name":"Medical Research Institute, The Holy Family Hospital, Nazareth 16100, Israel"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-4524-1505","authenticated-orcid":false,"given":"Ahmad","family":"Kadriya","sequence":"additional","affiliation":[{"name":"Medical Research Institute, The Holy Family Hospital, Nazareth 16100, Israel"},{"name":"Azrieli Faculty of Medicine, Bar-Ilan University, Safed 1311502, Israel"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-7436-3515","authenticated-orcid":false,"given":"Abraham O.","family":"Samson","sequence":"additional","affiliation":[{"name":"Azrieli Faculty of Medicine, Bar-Ilan University, Safed 1311502, Israel"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Mizied","family":"Falah","sequence":"additional","affiliation":[{"name":"Medical Research Institute, The Holy Family Hospital, Nazareth 16100, Israel"},{"name":"Azrieli Faculty of Medicine, Bar-Ilan University, Safed 1311502, Israel"}],"role":[{"role":"author","vocabulary":"crossref"}]}],"member":"1968","published-online":{"date-parts":[[2026,4,27]]},"reference":[{"key":"ref_1","first-page":"229","article-title":"Global cancer statistics 2022: GLOBOCAN estimates of incidence and mortality worldwide for 36 cancers in 185 countries","volume":"74","author":"Bray","year":"2024","journal-title":"CA A Cancer J. 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