{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,7,27]],"date-time":"2026-07-27T13:13:11Z","timestamp":1785157991588,"version":"3.55.0"},"reference-count":53,"publisher":"Frontiers Media SA","license":[{"start":{"date-parts":[[2026,3,20]],"date-time":"2026-03-20T00:00:00Z","timestamp":1773964800000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"content-domain":{"domain":["frontiersin.org"],"crossmark-restriction":true},"short-container-title":["Front. Pharmacol."],"abstract":"<jats:p>We previously reported that the heptamethine cyanine dye\u2013conjugated artesunate (DZ-1-ART) induces apoptosis in monolayer (2D) cell culture models. However, in 2D cultures, cells grow on flat, rigid plastic surfaces that fail to recapitulate the three-dimensional architecture of tumor tissues. This artificial environment alters cell polarity, morphology, and mechanical signaling, leading to non-physiological behavior. To overcome these limitations, we developed patient-derived tumoroids to assess the tumoricidal efficacy of the DZ-1-ART conjugate. In this study, tumoroids were established from fresh tissue samples of a malignant neoplasm of the sigmoid colon. The anticancer activity of DZ-1-ART was evaluated in these tumoroids. Propidium iodide staining confirmed DZ-1-ART\u2013induced cytotoxicity, while TUNEL and immunoblotting assays demonstrated that this cytotoxicity was mediated by apoptosis. Furthermore, MitoTracker staining and near-infrared fluorescence indicated mitochondrial localization of DZ-1-ART. The JC-1 assay showed disruption of mitochondrial membrane potential following DZ-1-ART treatment. Additionally, deferoxamine and MitoTEMPO pretreatment revealed that DZ-1-ART induced mitochondria-mediated reactive oxygen species (ROS) generation in tumoroids. Collectively, these findings suggest that DZ-1-ART acts as a potent mitochondria-targeting anticancer agent with potential for precision therapy.<\/jats:p>","DOI":"10.3389\/fphar.2026.1743141","type":"journal-article","created":{"date-parts":[[2026,3,20]],"date-time":"2026-03-20T06:39:00Z","timestamp":1773988740000},"update-policy":"https:\/\/doi.org\/10.3389\/crossmark-policy","source":"Crossref","is-referenced-by-count":1,"title":["DZ-1-artesunate conjugate induces mitochondria-mediated, reactive oxygen species-dependent apoptosis in colorectal cancer tumoroids"],"prefix":"10.3389","volume":"17","author":[{"given":"Badrinath","family":"Narayanasamy","sequence":"first","affiliation":[{"name":"Cedars-Sinai Cancer Institute and Department of Biomedical Sciences, Cedars-Sinai Medical Center","place":["Los Angeles, CA, United States"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Yi","family":"Zhang","sequence":"additional","affiliation":[{"name":"Cedars-Sinai Cancer Institute and Department of Biomedical Sciences, Cedars-Sinai Medical Center","place":["Los Angeles, CA, United States"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Alexandra","family":"Gangi","sequence":"additional","affiliation":[{"name":"Cedars-Sinai Cancer Institute and Department of Surgery, Cedars-Sinai Medical Center","place":["Los Angeles, CA, United States"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Robert","family":"Figlin","sequence":"additional","affiliation":[{"name":"Cedars-Sinai Cancer Institute and Division of Hematology, Cedars-Sinai Medical Center","place":["Los Angeles, CA, United States"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Karine","family":"Sargsyan","sequence":"additional","affiliation":[{"name":"Cedars-Sinai Cancer Institute and Department of Biomedical Sciences, Cedars-Sinai Medical Center","place":["Los Angeles, CA, United States"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Heuiran","family":"Lee","sequence":"additional","affiliation":[{"name":"Bio-Medical Institute of Technology, College of Medicine, University of Ulsan","place":["Seoul, Republic of Korea"]},{"name":"Department of Microbiology, Asan Medical Center, College of Medicine, University of Ulsan","place":["Seoul, Republic of Korea"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Cheryn","family":"Song","sequence":"additional","affiliation":[{"name":"Bio-Medical Institute of Technology, College of Medicine, University of Ulsan","place":["Seoul, Republic of Korea"]},{"name":"Department of Urology, Asan Medical Center, College of Medicine, University of Ulsan","place":["Seoul, Republic of Korea"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Yong J.","family":"Lee","sequence":"additional","affiliation":[{"name":"Cedars-Sinai Cancer Institute and Department of Biomedical Sciences, Cedars-Sinai Medical Center","place":["Los Angeles, CA, United States"]}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"1965","published-online":{"date-parts":[[2026,3,20]]},"reference":[{"key":"B1","doi-asserted-by":"publisher","first-page":"100114","DOI":"10.1016\/j.adcanc.2024.100114","article-title":"Multi drug resistance in colorectal Cancer-approaches to overcome, advancements and future success","volume":"10","author":"Ashique","year":"2024","journal-title":"Adv. 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