{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,5,16]],"date-time":"2026-05-16T09:16:00Z","timestamp":1778922960962,"version":"3.51.4"},"reference-count":67,"publisher":"Wiley","issue":"4","license":[{"start":{"date-parts":[[2026,3,27]],"date-time":"2026-03-27T00:00:00Z","timestamp":1774569600000},"content-version":"vor","delay-in-days":0,"URL":"http:\/\/creativecommons.org\/licenses\/by\/4.0\/"},{"start":{"date-parts":[[2026,3,27]],"date-time":"2026-03-27T00:00:00Z","timestamp":1774569600000},"content-version":"tdm","delay-in-days":0,"URL":"http:\/\/doi.wiley.com\/10.1002\/tdm_license_1.1"}],"content-domain":{"domain":["onlinelibrary.wiley.com"],"crossmark-restriction":true},"short-container-title":["Chem Biol Drug Des"],"published-print":{"date-parts":[[2026,4]]},"abstract":"<jats:title>ABSTRACT<\/jats:title>\n                  <jats:p>Hepatocellular carcinoma is one of the most aggressive malignancies worldwide, with limited treatment options and high resistance to conventional therapies. Developing novel therapeutic strategies that target alternative cell death mechanisms is crucial for overcoming treatment resistance. This study evaluated the cytotoxicity of eight sulfonated silver(I) and gold(I) N\u2010heterocyclic carbene (NHC) complexes\u2014four newly synthesized\u2014against human liver cancer cells and investigated the mechanisms of the compounds that exhibited higher selectivity for cancer cells compared to non\u2010malignant liver cells. Morphological analysis revealed distinct features of autophagy rather than apoptosis, as confirmed by the absence of chromatin condensation, caspase\u20103 activation, and PARP\u20101 cleavage. Instead, both complexes strongly upregulated Beclin\u20101 and LC3\u2010II expression\u2014key autophagy markers\u2014while inhibiting the AKT\/mTOR signaling pathway. The observed cytotoxic effects were associated with a significant increase in reactive oxygen species (ROS) production. Pre\u2010treatment with the antioxidant N\u2010acetyl\u2010L\u2010cysteine completely abolished both cytotoxicity and autophagy induction. These findings demonstrate that silver(I) and gold(I) NHC complexes induce ROS\u2010dependent autophagic cell death in this kind of cancer cells. The ability of these compounds to trigger non\u2010apoptotic cell death mechanisms highlights their potential as promising candidates for overcoming apoptosis resistance in HCC therapy, warranting further in\u00a0vivo investigations.<\/jats:p>","DOI":"10.1111\/cbdd.70283","type":"journal-article","created":{"date-parts":[[2026,3,28]],"date-time":"2026-03-28T04:25:37Z","timestamp":1774671937000},"update-policy":"https:\/\/doi.org\/10.1002\/crossmark_policy","source":"Crossref","is-referenced-by-count":0,"title":["Novel Silver(I) and Gold(I) N\u2010Heterocyclic Carbene Complexes Induce\n                    <scp>ROS<\/scp>\n                    \u2010Dependent Autophagic Cell Death in Human Hepatoma Cell Line\n                    <scp>HepG2<\/scp>"],"prefix":"10.1111","volume":"107","author":[{"ORCID":"https:\/\/orcid.org\/0000-0001-6682-1459","authenticated-orcid":false,"given":"Rocchina","family":"Miglionico","sequence":"first","affiliation":[{"name":"Department of Health Sciences 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