{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,8,12]],"date-time":"2026-08-12T20:28:46Z","timestamp":1786566526677,"version":"build-2736575974"},"reference-count":38,"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:\/\/onlinelibrary.wiley.com\/termsAndConditions#vor"},{"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":["J Biochem &amp;amp; Molecular Tox"],"published-print":{"date-parts":[[2026,4]]},"abstract":"<jats:title>ABSTRACT<\/jats:title>\n                  <jats:p>Renal cell carcinoma (RCC) is a common urologic malignancy with limited treatment options. The neuropeptide vasoactive intestinal peptide (VIP) regulates diverse biological processes by binding to VPAC1 and VPAC2 receptors, but its role in RCC remains unclear. The proliferation of RCC Caki\u20101 cells was evaluated using the Cell Counting Kit\u20108 (CCK\u20108), while lactate dehydrogenase (LDH) and \u03b3\u2010glutamyl transpeptidase (\u03b3\u2010GPT) release were measured using commercial kits. Reactive oxygen species (ROS) levels were analyzed via dihydroethidium (DHE) staining. Superoxide dismutase (SOD) activity and malondialdehyde (MDA) levels were quantified using commercial assay kits. Autophagy was assessed through monodansylcadaverine (MDC) staining, and the expression levels of related mRNAs and proteins were quantified by RT\u2010PCR and Western blotting, respectively. VIP treatment (0\u201350\u2009\u03bcM) exhibited dose\u2010dependent cytotoxic effects, including reduced cell viability, increased LDH and \u03b3\u2010GPT release, and induction of oxidative stress as evidenced by elevated ROS and MDA levels with concomitant decrease in SOD2 activity. At concentrations of 5\u201310\u2009\u03bcM, VIP induced autophagic responses characterized by enhanced MDC staining, increased microtubule\u2010associated protein 1 light chain 3 (LC3)\u2010II\/LC3\u2010I ratio, upregulated Beclin1 expression, and accelerated p62 degradation. Mechanistically, VIP\u2010mediated autophagy was associated with sirtuin 3 (SIRT3) downregulation and increased Ac\u2010FOXO1 levels, with SIRT3 overexpression effectively counteracting the VIP\u2010induced autophagic effects. Our findings demonstrate that VIP induces both cytotoxic effects and autophagy in VPAC1\u2010expressing RCC cells through modulation of the SIRT3\/FOXO1 signaling pathway, highlighting its potential therapeutic value for renal cell carcinoma.<\/jats:p>","DOI":"10.1002\/jbt.70815","type":"journal-article","created":{"date-parts":[[2026,3,27]],"date-time":"2026-03-27T11:55:44Z","timestamp":1774612544000},"update-policy":"https:\/\/doi.org\/10.1002\/crossmark_policy","source":"Crossref","is-referenced-by-count":0,"title":["Vasoactive Intestinal Peptide Induces Autophagy and Cytotoxicity in Renal Cell Carcinoma via SIRT3\u2010Dependent Signaling Pathway"],"prefix":"10.1002","volume":"40","author":[{"ORCID":"https:\/\/orcid.org\/0009-0000-6131-8539","authenticated-orcid":false,"given":"Liangliang","family":"Li","sequence":"first","affiliation":[{"name":"Department of Urological Oncology The First Affiliated Hospital of Henan University of Science and Technology Luoyang 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