{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,7,3]],"date-time":"2026-07-03T21:26:01Z","timestamp":1783113961581,"version":"3.54.6"},"reference-count":46,"publisher":"Wiley","issue":"2","license":[{"start":{"date-parts":[[2024,8,15]],"date-time":"2024-08-15T00:00:00Z","timestamp":1723680000000},"content-version":"vor","delay-in-days":14,"URL":"http:\/\/creativecommons.org\/licenses\/by-nc\/4.0\/"}],"content-domain":{"domain":["onlinelibrary.wiley.com"],"crossmark-restriction":true},"short-container-title":["Chem Biol Drug Des"],"published-print":{"date-parts":[[2024,8]]},"abstract":"<jats:title>ABSTRACT<\/jats:title><jats:p>Cancer is a serious global health problem, causing the loss of millions of lives each year. Plumbagin, a compound derived from the medicinal plant <jats:italic>Plumbago zeylanica<\/jats:italic>, has shown promise in stopping the growth of tumor cells both in laboratory settings and in living organisms. Many plant\u2010based compounds exert their effects through copper's ability to produce reactive oxygen species (ROS). This study aimed to understand how plumbagin, dependent on copper, induces cell death (apoptosis) in human cancer cells through various experiments. The results demonstrate that plumbagin hinders the growth of pancreatic cancer cells PNAC\u20101 and MIA PaCa\u20102 by utilizing the copper naturally present in the cells. Unlike metal chelators that remove iron and zinc (desferrioxamine mesylate and histidine), a specific copper chelator called neocuproine lessens the cell death caused by plumbagin. When ROS scavengers are used, plumbagin\u2010induced apoptosis is inhibited, indicating that ROS plays a role in initiating cell death. The study also proves that plumbagin prevents copper from leaving cancer cells by suppressing the expression of specific genes (<jats:italic>CTR1<\/jats:italic> and <jats:italic>ATP7A<\/jats:italic>). It is confirmed that plumbagin targets the nuclear copper, leading to signals that promote oxidative stress and, ultimately, cell death. These findings provide valuable insights into the potential of plumbagin as a substance to combat cancer, highlighting the importance of understanding how copper behaves within cancer cells.<\/jats:p>","DOI":"10.1111\/cbdd.14606","type":"journal-article","created":{"date-parts":[[2024,8,16]],"date-time":"2024-08-16T03:09:05Z","timestamp":1723777745000},"update-policy":"https:\/\/doi.org\/10.1002\/crossmark_policy","source":"Crossref","is-referenced-by-count":4,"title":["Plumbagin's Antiproliferative Mechanism in Human Cancer Cells: A Copper\u2010Dependent Cytotoxic Approach"],"prefix":"10.1111","volume":"104","author":[{"ORCID":"https:\/\/orcid.org\/0000-0001-5193-0759","authenticated-orcid":false,"given":"Mohamed","family":"El\u00a0Oirdi","sequence":"first","affiliation":[{"name":"Department of Life Sciences, College of Science King Faisal University  Al Ahsa Saudi Arabia"},{"name":"Department of Basic Sciences, Preparatory Year King\u00a0Faisal University  Al Ahsa Saudi 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