{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2025,10,24]],"date-time":"2025-10-24T00:58:14Z","timestamp":1761267494524,"version":"build-2065373602"},"reference-count":38,"publisher":"MDPI AG","issue":"20","license":[{"start":{"date-parts":[[2025,10,21]],"date-time":"2025-10-21T00:00:00Z","timestamp":1761004800000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":["IJMS"],"abstract":"<jats:p>Pancreatic cancer is an extremely deadly disease with few effective treatment options and the lowest survival rate among all types of cancer. As a result, there is an urgent need for the development of new and more effective treatment strategies. Natural products have long been a vital source of drug discovery, offering unique bioactive compounds, and representing a promising source for new, effective, and less toxic treatments. In the present study, we aimed to investigate the effects of Apteranthes europaea (Guss.) Murb (A. europaea) root extract on the growth of pancreatic cancer cells. The proliferation assay (XTT) and real-time analysis using the IncuCyte Live-Cell Analysis System, following treatment of PL45 and Mia PaCa-2 pancreatic cancer cells with escalating concentrations (50\u2013200 \u00b5L) to A. europaea root extract, demonstrated the progression of apoptosis. Apoptosis induction was confirmed through cell cycle analysis and Annexin V\/PI double staining assays. Western blot analysis revealed the distinct activation of caspase-8, accompanied by the cleavage of caspase-3 and Poly (ADP-ribose) polymerase (PARP). Interestingly, no activation of caspase-9 was observed, suggesting the involvement of the extrinsic apoptotic pathway. Our findings suggest that A. europaea extract may be a potential novel strategy for treating pancreatic cancer.<\/jats:p>","DOI":"10.3390\/ijms262010221","type":"journal-article","created":{"date-parts":[[2025,10,21]],"date-time":"2025-10-21T13:42:03Z","timestamp":1761054123000},"page":"10221","update-policy":"https:\/\/doi.org\/10.3390\/mdpi_crossmark_policy","source":"Crossref","is-referenced-by-count":0,"title":["Induction of Extrinsic Apoptotic Pathway in Pancreatic Cancer Cells by Apteranthes europaea Root Extract"],"prefix":"10.3390","volume":"26","author":[{"ORCID":"https:\/\/orcid.org\/0000-0001-8115-2388","authenticated-orcid":false,"given":"Rinat","family":"Bar-Shalom","sequence":"first","affiliation":[{"name":"Department of Human Biology, Faculty of Natural Sciences, University of Haifa, Mount Carmel, Haifa 3498838, Israel"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Lana","family":"Abdelhak","sequence":"additional","affiliation":[{"name":"Department of Human Biology, Faculty of Natural Sciences, University of Haifa, Mount Carmel, Haifa 3498838, Israel"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"ORCID":"https:\/\/orcid.org\/0009-0005-3567-8908","authenticated-orcid":false,"given":"Wafa","family":"Zennouhi","sequence":"additional","affiliation":[{"name":"Team of Ethnopharmacology and Pharmacognosy, Biology Department, Faculty of Sciences and Techniques, Moulay Ismail University of Meknes, 52000 Errachidia, Morocco"},{"name":"Biology Unit and Molecular Research, Department of Life Sciences, National Center for Energy, Sciences, and Nuclear Techniques (CNESTEN), P.O. Box 1382, 10001 Rabat, Morocco"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Farid","family":"Khallouki","sequence":"additional","affiliation":[{"name":"Team of Ethnopharmacology and Pharmacognosy, Biology Department, Faculty of Sciences and Techniques, Moulay Ismail University of Meknes, 52000 Errachidia, Morocco"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Laila","family":"Benbacer","sequence":"additional","affiliation":[{"name":"Biology Unit and Molecular Research, Department of Life Sciences, National Center for Energy, Sciences, and Nuclear Techniques (CNESTEN), P.O. Box 1382, 10001 Rabat, Morocco"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Fuad","family":"Fares","sequence":"additional","affiliation":[{"name":"Department of Human Biology, Faculty of Natural Sciences, University of Haifa, Mount Carmel, Haifa 3498838, Israel"}],"role":[{"role":"author","vocabulary":"crossref"}]}],"member":"1968","published-online":{"date-parts":[[2025,10,21]]},"reference":[{"key":"ref_1","doi-asserted-by":"crossref","first-page":"2913","DOI":"10.1158\/0008-5472.CAN-14-0155","article-title":"Projecting Cancer Incidence and Deaths to 2030: The Unexpected Burden of Thyroid, Liver, and Pancreas Cancers in the United States","volume":"74","author":"Rahib","year":"2014","journal-title":"Cancer Res."},{"key":"ref_2","doi-asserted-by":"crossref","first-page":"1729","DOI":"10.1016\/j.cell.2023.02.014","article-title":"Pancreatic Cancer: Advances and Challenges","volume":"186","author":"Halbrook","year":"2023","journal-title":"Cell"},{"key":"ref_3","doi-asserted-by":"crossref","first-page":"422","DOI":"10.1016\/j.ejca.2021.02.023","article-title":"Nab-paclitaxel\/gemcitabine combination is more effective than gemcitabine alone in locally advanced, unresectable pancreatic cancer\u2014A GISCAD phase II randomized trial","volume":"148","author":"Cascinu","year":"2021","journal-title":"Eur. 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