{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,6,26]],"date-time":"2026-06-26T02:48:32Z","timestamp":1782442112010,"version":"3.54.5"},"reference-count":36,"publisher":"MDPI AG","issue":"10","license":[{"start":{"date-parts":[[2026,5,21]],"date-time":"2026-05-21T00:00:00Z","timestamp":1779321600000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"funder":[{"DOI":"10.13039\/501100001691","name":"Grant-in-Aid from the JSPS Core-to-Core Program","doi-asserted-by":"publisher","award":["JPJSCCB20230005"],"award-info":[{"award-number":["JPJSCCB20230005"]}],"id":[{"id":"10.13039\/501100001691","id-type":"DOI","asserted-by":"publisher"}]}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":["IJMS"],"abstract":"<jats:p>Colorectal cancer remains a global health challenge due to its high mortality and therapy resistance. While Wedelia trilobata (L.) (WT) exhibits pharmacological potential, its specific mechanisms against this cancer are not fully understood. We investigated the anticancer effects of W. trilobata leaf ethanol extract and its n-hexane and chloroform fractions on HT-29 cells. The WT extract significantly inhibited proliferation by inducing G1\/S phase arrest and downregulating PCNA mRNA. It triggered substantial DNA damage (increased \u03b3-H2AX) and suppressed the mitogen-activated protein kinase (ERK) pathway. Notably, the WT extract-induced autophagy-mediated cell death, marked by acidic vesicular organelle formation and increased LC3-II levels. Inhibition of autophagy with N-acetylcysteine and 3-methyladenine partially rescued cell viability, restored p-Akt levels, and reduced LC3-II, indicating that cell death is regulated via the ROS-mediated Akt\/mTOR signaling axis. Additionally, autophagic flux was validated using chloroquine, which led to a synergistic accumulation of LC3-II. GC-MS analysis identified 48 and 52 compounds in the n-hexane and chloroform fractions, respectively, including metabolites with known antioxidant and antitumoral properties. These findings demonstrate that W. trilobata induces autophagic cell death through ROS-mediated Akt\/mTOR inhibition, supporting its potential as a source of innovative colorectal cancer therapeutics.<\/jats:p>","DOI":"10.3390\/ijms27104636","type":"journal-article","created":{"date-parts":[[2026,5,21]],"date-time":"2026-05-21T13:53:24Z","timestamp":1779371604000},"page":"4636","update-policy":"https:\/\/doi.org\/10.3390\/mdpi_crossmark_policy","source":"Crossref","is-referenced-by-count":1,"title":["Wedelia trilobata (L.) Leaf Extract Induces Autophagy-Mediated Cell Death in HT-29 Colorectal Cancer Cells via Suppression of the Akt\/mTOR Signaling Axis"],"prefix":"10.3390","volume":"27","author":[{"given":"Tue Minh","family":"Duong","sequence":"first","affiliation":[{"name":"Department of Functional Chemistry, Kyoto Institute of Technology, Kyoto 606-8585, Japan"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-5128-4654","authenticated-orcid":false,"given":"Thanh Chau Quoc","family":"Nguyen","sequence":"additional","affiliation":[{"name":"Faculty of Chemistry, College of Natural Sciences, Can Tho University Campus II, 3\/2 Street, Ninh Kieu Ward, Can Tho City 94000, Vietnam"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-1342-3657","authenticated-orcid":false,"given":"Tomonori","family":"Waku","sequence":"additional","affiliation":[{"name":"Department of Functional Chemistry, Kyoto Institute of Technology, Kyoto 606-8585, Japan"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-0142-9613","authenticated-orcid":false,"given":"Kenji","family":"Kanaori","sequence":"additional","affiliation":[{"name":"Department of Functional Chemistry, Kyoto Institute of Technology, Kyoto 606-8585, Japan"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-7496-4692","authenticated-orcid":false,"given":"Kaeko","family":"Kamei","sequence":"additional","affiliation":[{"name":"Department of Functional Chemistry, Kyoto Institute of Technology, Kyoto 606-8585, Japan"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"1968","published-online":{"date-parts":[[2026,5,21]]},"reference":[{"key":"ref_1","first-page":"7","article-title":"Cancer Statistics, 2020","volume":"70","author":"Siegel","year":"2020","journal-title":"CA Cancer J. 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