{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,7,28]],"date-time":"2026-07-28T09:58:29Z","timestamp":1785232709193,"version":"3.55.0"},"reference-count":45,"publisher":"MDPI AG","issue":"8","license":[{"start":{"date-parts":[[2026,7,28]],"date-time":"2026-07-28T00:00:00Z","timestamp":1785196800000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":["Life"],"abstract":"<jats:p>Colorectal cancer (CRC) is a leading cause of cancer death, with resistance and apoptosis evasion\u2014often via Bcl-2\u2014representing major challenges. The redox-modulating drug dimethyl fumarate (DMF) has demonstrated efficacy in hematologic malignancies; however, its potential in solid tumors remains unclear. Here, we show that DMF, especially in combination with the Bcl-2 inhibitor venetoclax (ABT-199), induces apoptosis in HCT-116 CRC cells. DMF impairs mitochondrial respiration, causing membrane hyperpolarization, ATP depletion, autophagy, and cell cycle arrest. Combined treatment increases metabolic stress, reduces proliferation, and induces sustained G2 arrest with downregulation of cyclins and CDKs. These findings highlight a combined effect targeting redox balance and apoptosis in CRC. Given their clinical availability, DMF and ABT-199 represent a promising combination for further preclinical evaluation.<\/jats:p>","DOI":"10.3390\/life16081250","type":"journal-article","created":{"date-parts":[[2026,7,28]],"date-time":"2026-07-28T08:52:01Z","timestamp":1785228721000},"page":"1250","update-policy":"https:\/\/doi.org\/10.3390\/mdpi_crossmark_policy","source":"Crossref","is-referenced-by-count":0,"title":["Dimethyl Fumarate Enhances Venetoclax-Induced Cell Death by Inhibiting Mitochondrial Respiration and Cell Cycle Control in Colorectal Cancer"],"prefix":"10.3390","volume":"16","author":[{"given":"Simon","family":"Wagner","sequence":"first","affiliation":[{"name":"Department of Internal Medicine I, Gastroenterology, Hepatology, Endocrinology, Rheumatology and Infectious Diseases, University Hospital Regensburg, Franz-Josef-Strau\u00df-Alle 11, 93053 Regensburg, Germany"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Anne","family":"Schroeder","sequence":"additional","affiliation":[{"name":"Translational Oncology (TRON) at the University Medical Center of Johannes Gutenberg University, Freiligrathstra\u00dfe 12, 55131 Mainz, Germany"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-9284-1138","authenticated-orcid":false,"given":"Sara Martina","family":"Steinmann","sequence":"additional","affiliation":[{"name":"Department of Internal Medicine I, Gastroenterology, Hepatology, Endocrinology, Rheumatology and Infectious Diseases, University Hospital Regensburg, Franz-Josef-Strau\u00df-Alle 11, 93053 Regensburg, Germany"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Claudia","family":"Kunst","sequence":"additional","affiliation":[{"name":"Department of Internal Medicine I, Gastroenterology, Hepatology, Endocrinology, Rheumatology and Infectious Diseases, University Hospital Regensburg, Franz-Josef-Strau\u00df-Alle 11, 93053 Regensburg, Germany"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Kirstin","family":"Pollinger","sequence":"additional","affiliation":[{"name":"Department of Internal Medicine I, Gastroenterology, Hepatology, Endocrinology, Rheumatology and Infectious Diseases, University Hospital Regensburg, Franz-Josef-Strau\u00df-Alle 11, 93053 Regensburg, Germany"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Manuela","family":"Gunckel","sequence":"additional","affiliation":[{"name":"Department of Internal Medicine I, Gastroenterology, Hepatology, Endocrinology, Rheumatology and Infectious Diseases, University Hospital Regensburg, Franz-Josef-Strau\u00df-Alle 11, 93053 Regensburg, Germany"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Elisabeth","family":"Aschenbrenner","sequence":"additional","affiliation":[{"name":"Department of Internal Medicine I, Gastroenterology, Hepatology, Endocrinology, Rheumatology and Infectious Diseases, University Hospital Regensburg, Franz-Josef-Strau\u00df-Alle 11, 93053 Regensburg, Germany"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-8520-4568","authenticated-orcid":false,"given":"Martina","family":"M\u00fcller","sequence":"additional","affiliation":[{"name":"Department of Internal Medicine I, Gastroenterology, Hepatology, Endocrinology, Rheumatology and Infectious Diseases, University Hospital Regensburg, Franz-Josef-Strau\u00df-Alle 11, 93053 Regensburg, Germany"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0009-0006-2897-3447","authenticated-orcid":false,"given":"Karsten","family":"G\u00fclow","sequence":"additional","affiliation":[{"name":"Department of Internal Medicine I, Gastroenterology, Hepatology, Endocrinology, Rheumatology and Infectious Diseases, University Hospital Regensburg, Franz-Josef-Strau\u00df-Alle 11, 93053 Regensburg, Germany"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"1968","published-online":{"date-parts":[[2026,7,28]]},"reference":[{"key":"ref_1","first-page":"229","article-title":"Global cancer statistics 2022: GLOBOCAN estimates of incidence and mortality worldwide for 36 cancers in 185 countries","volume":"74","author":"Bray","year":"2024","journal-title":"CA Cancer J. 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