{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,11,3]],"date-time":"2026-11-03T22:09:51Z","timestamp":1793743791586,"version":"4.6.1"},"reference-count":41,"publisher":"MDPI AG","issue":"4","license":[{"start":{"date-parts":[[2026,4,21]],"date-time":"2026-04-21T00:00:00Z","timestamp":1776729600000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"funder":[{"DOI":"10.13039\/501100003725","name":"National Research Foundation of Korea","doi-asserted-by":"crossref","award":["RS-2018-NR033232"],"award-info":[{"award-number":["RS-2018-NR033232"]}],"id":[{"id":"10.13039\/501100003725","id-type":"DOI","asserted-by":"crossref"}]},{"DOI":"10.13039\/501100003725","name":"National Research Foundation of Korea","doi-asserted-by":"crossref","award":["RS-2022-NR067329"],"award-info":[{"award-number":["RS-2022-NR067329"]}],"id":[{"id":"10.13039\/501100003725","id-type":"DOI","asserted-by":"crossref"}]},{"award":["RS-2018-NR033232"],"award-info":[{"award-number":["RS-2018-NR033232"]}],"id":[{"id":"https:\/\/ror.org\/013aysd81","id-type":"ROR","asserted-by":"publisher"}]},{"award":["RS-2022-NR067329"],"award-info":[{"award-number":["RS-2022-NR067329"]}],"id":[{"id":"https:\/\/ror.org\/013aysd81","id-type":"ROR","asserted-by":"publisher"}]}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":["Antioxidants"],"abstract":"<jats:p>Neuroblastoma remains a formidable pediatric malignancy characterized by profound metabolic plasticity and limited therapeutic responsiveness in high-risk disease. Emerging evidence positions the interplay between Reactive Oxygen Species (ROS) and the metabolic sentinel AMP-activated protein kinase (AMPK) as a critical regulator of tumor metabolic stress and apoptotic susceptibility, with additional implications in the systemic pathology of Cancer Cachexia. Building on our previous work demonstrating that 1,1-Diethoxyethane (1,1-DEE; Biosacetalin), a volatile aroma compound inhibits mitochondrial complex I, induces ROS production, and activates AMPK-PGC1\u03b1-mediated mitochondrial biogenesis accompanying enhancement of aerobic respiration, leading to anti-Warburg effect. We identify 1,1-DEE as a previously unrecognized metabolic modulator with potent antitumor activity. 1,1-DEE triggers ROS-induced AMPK activation, leading to apoptotic elimination of neuroblastoma cells (SH-SY5Y), robust suppression of tumor growth, and significant prolongation of survival (median survival 77 days) in tumor-bearing NSG mice. Strikingly, 1,1-DEE simultaneously alleviates cancer-associated cachexia by preserving body weight. Mechanistically, our findings reveal a ROS\u2013AMPK\u2013centered signaling axis through which 1,1-DEE integrates tumor-selective cytotoxicity with systemic metabolic protection, highlighting a unified therapeutic strategy for targeting both tumor progression and cachexia in neuroblastoma.<\/jats:p>","DOI":"10.3390\/antiox15040521","type":"journal-article","created":{"date-parts":[[2026,4,22]],"date-time":"2026-04-22T09:01:24Z","timestamp":1776848484000},"page":"521","update-policy":"https:\/\/doi.org\/10.3390\/mdpi_crossmark_policy","source":"Crossref","is-referenced-by-count":2,"title":["Biosacetalin (1,1-Diethoxyethane) Prolongs Survival and Alleviates Cachexia in the NSG Mice Bearing Neuroblastoma SH-SY5Y Cells"],"prefix":"10.3390","volume":"15","author":[{"given":"Dhiraj Kumar","family":"Sah","sequence":"first","affiliation":[{"name":"Department of Biochemistry, Research Center for Aging and Geriatrics, Research Institute of Medical Sciences, Chonnam National University Medical School, Gwangju 61469, Republic of Korea"},{"name":"Department of Biomedical Sciences, Research Center for Aging and Geriatrics, Research Institute of Medical Sciences, Chonnam National University Medical School, Gwangju 61469, Republic of Korea"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Thang","family":"Nguyen Huu","sequence":"additional","affiliation":[{"name":"Department of Biochemistry, Research Center for Aging and Geriatrics, Research Institute of Medical Sciences, Chonnam National University Medical School, Gwangju 61469, Republic of Korea"},{"name":"Department of Biomedical Sciences, Research Center for Aging and Geriatrics, Research Institute of Medical Sciences, Chonnam National University Medical School, Gwangju 61469, Republic of Korea"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Jin Myung","family":"Choi","sequence":"additional","affiliation":[{"name":"Luxanima Inc., Room 102, 12-55, Sandan-gil, Hwasun-eup, Hwasun-gun 58128, Republic of Korea"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Vu Hoang","family":"Trinh","sequence":"additional","affiliation":[{"name":"Department of Biochemistry, Research Center for Aging and Geriatrics, Research Institute of Medical Sciences, Chonnam National University Medical School, Gwangju 61469, Republic of Korea"},{"name":"Department of Biomedical Sciences, Research Center for Aging and Geriatrics, Research Institute of Medical Sciences, Chonnam National University Medical School, Gwangju 61469, Republic of Korea"},{"name":"Department of Oncology, Pham Ngoc Thach University of Medicine, Ho Chi Minh City 700000, Vietnam"},{"name":"Department of Medical Sciences, Pham Ngoc Thach University of Medicine, Ho Chi Minh City 700000, Vietnam"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Hyun Joong","family":"Yoon","sequence":"additional","affiliation":[{"name":"Department of Biochemistry, Research Center for Aging and Geriatrics, Research Institute of Medical Sciences, Chonnam National University Medical School, Gwangju 61469, Republic of Korea"},{"name":"Department of Biomedical Sciences, Research Center for Aging and Geriatrics, Research Institute of Medical Sciences, Chonnam National University Medical School, Gwangju 61469, Republic of Korea"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Seung-Rock","family":"Lee","sequence":"additional","affiliation":[{"name":"Department of Biochemistry, Research Center for Aging and Geriatrics, Research Institute of Medical Sciences, Chonnam National University Medical School, Gwangju 61469, Republic of Korea"},{"name":"Department of Biomedical Sciences, Research Center for Aging and Geriatrics, Research Institute of Medical Sciences, Chonnam National University Medical School, Gwangju 61469, Republic of Korea"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"1968","published-online":{"date-parts":[[2026,4,21]]},"reference":[{"key":"ref_1","doi-asserted-by":"crossref","first-page":"2904","DOI":"10.1002\/cncr.34847","article-title":"Neurocognitive outcomes in adult survivors of neuroblastoma: A report from the Childhood Cancer Survivor Study","volume":"129","author":"Hesko","year":"2023","journal-title":"Cancer"},{"key":"ref_2","doi-asserted-by":"crossref","unstructured":"Mastronuzzi, A., Colafati, G.S., Carai, A., D\u2019Egidio, M., Fabozzi, F., Del Bufalo, F., Villani, M.F., Del Baldo, G., Vennarini, S., and Canino, C. 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