{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,10,21]],"date-time":"2026-10-21T17:14:48Z","timestamp":1792602888496,"version":"4.5.0"},"reference-count":78,"publisher":"MDPI AG","issue":"21","license":[{"start":{"date-parts":[[2024,10,30]],"date-time":"2024-10-30T00:00:00Z","timestamp":1730246400000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"funder":[{"name":"Modern Agroindustry Technology Research System from the Ministry of Agriculture of China","award":["CARS-44"],"award-info":[{"award-number":["CARS-44"]}]}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":["IJMS"],"abstract":"<jats:p>Melittin has previously been found to have a positive effect on colorectal cancer (CRC) treatment, one of the most difficult-to-treat malignancies, but the mechanism by which this effect occurs remains unclear. We evaluated melittin\u2019s pro-apoptotic and anti-metastatic effects on CRC in vitro and in vivo. The results showed that melittin-induced mitochondrial ROS bursts decreased \u0394\u03a8m, inhibited Bcl-2 expression, and increased Bax expression in both cells and tumor tissues. This led to increased mitochondrial membrane permeability and the release of pro-apoptotic factors, particularly the high expression of Cytochrome C, initiating the apoptosis program. Additionally, through wound-healing and transwell assays, melittin inhibited the migration and invasion of CRC cells. In vivo, the anti-metastatic effect of melittin was also verified in a lung metastasis mouse model. Western blotting and immunohistochemistry analysis indicated that melittin suppressed the expression of MMPs and regulated the expression of crucial EMT markers and related transcription factors, thereby inhibiting EMT. Furthermore, the melittin disrupts neovascularization, ultimately inhibiting the metastasis of CRC. In conclusion, melittin exerts anti-CRC effects by promoting apoptosis and inhibiting metastasis, providing a theoretical basis for further research on melittin as a targeted therapeutic agent for CRC.<\/jats:p>","DOI":"10.3390\/ijms252111686","type":"journal-article","created":{"date-parts":[[2024,10,31]],"date-time":"2024-10-31T06:55:37Z","timestamp":1730357737000},"page":"11686","update-policy":"https:\/\/doi.org\/10.3390\/mdpi_crossmark_policy","source":"Crossref","is-referenced-by-count":22,"title":["Melittin Inhibits Colorectal Cancer Growth and Metastasis by Ac-Tivating the Mitochondrial Apoptotic Pathway and Suppressing Epithelial\u2013Mesenchymal Transition and Angiogenesis"],"prefix":"10.3390","volume":"25","author":[{"given":"Kangli","family":"Wang","sequence":"first","affiliation":[{"name":"College of Animal Sciences, Zhejiang University, Hangzhou 310058, China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Lingchen","family":"Tao","sequence":"additional","affiliation":[{"name":"College of Animal Sciences, Zhejiang University, Hangzhou 310058, China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Meifei","family":"Zhu","sequence":"additional","affiliation":[{"name":"College of Animal Sciences, Zhejiang University, Hangzhou 310058, China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Xinyu","family":"Yu","sequence":"additional","affiliation":[{"name":"College of Animal Sciences, Zhejiang University, Hangzhou 310058, China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Yuanyuan","family":"Lu","sequence":"additional","affiliation":[{"name":"College of Animal Sciences, Zhejiang University, Hangzhou 310058, China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Bin","family":"Yuan","sequence":"additional","affiliation":[{"name":"College of Animal Sciences, Zhejiang University, Hangzhou 310058, China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Fuliang","family":"Hu","sequence":"additional","affiliation":[{"name":"College of Animal Sciences, Zhejiang University, Hangzhou 310058, China"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"1968","published-online":{"date-parts":[[2024,10,30]]},"reference":[{"key":"ref_1","doi-asserted-by":"crossref","first-page":"394","DOI":"10.3322\/caac.21492","article-title":"Global cancer statistics 2018: GLOBOCAN estimates of incidence and mortality worldwide for 36 cancers in 185 countries","volume":"68","author":"Bray","year":"2018","journal-title":"CA Cancer J. 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