{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,10,14]],"date-time":"2026-10-14T16:20:22Z","timestamp":1791994822546,"version":"4.4.0"},"reference-count":33,"publisher":"MDPI AG","issue":"1","license":[{"start":{"date-parts":[[2022,12,23]],"date-time":"2022-12-23T00:00:00Z","timestamp":1671753600000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"funder":[{"DOI":"10.13039\/501100001809","name":"National Natural Science Foundation of China","doi-asserted-by":"publisher","award":["82274198"],"award-info":[{"award-number":["82274198"]}],"id":[{"id":"10.13039\/501100001809","id-type":"DOI","asserted-by":"publisher"}]}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":["Pharmaceutics"],"abstract":"<jats:p>Celastrol, an active triterpenoid extracted from one of the most famous traditional Chinese medicines (TCMs), Tripterygium wilfordii Hook.f., is a novel anti-cancer drug with significant anti-angiogenesis activity. However, the exact molecular mechanisms underlying its anti-tumor angiogenesis effect remain unclear. The process of angiogenesis needs lots of energy supply, which mostly derives from mitochondria, the \u201cenergy factory\u201d in our body. This study shows that celastrol exerts visible suppression on tumor growth and angiogenesis in a cell-derived xenograft (CDX). Likewise, it reduced the tube formation and migration of human umbilical vein endothelial cells (HUVECs), suppressed the energy metabolism of mitochondria in the Seahorse XF Mito Stress Test, and triggered mitochondrial fragmentation and NF-\u03baB activation. Mechanically, celastrol downregulated the expression of mitochondrial-sharping protein optic atrophy protein 1 (OPA1), which was further estimated by the OPA1 knockdown model of HUVECs. Specifically, celastrol directly suppressed OPA1 at the mRNA level by inhibiting the phosphorylation of STAT3, and stattic (STAT3 inhibitor) showed the same effects on OPA1 suppression and anti-angiogenesis activity. Overall, this study indicates that celastrol inhibits tumor angiogenesis by suppressing mitochondrial function and morphology via the STAT3\/OPA1\/P65 pathway and provides new insight for mitochondrion-targeted cancer therapy.<\/jats:p>","DOI":"10.3390\/pharmaceutics15010048","type":"journal-article","created":{"date-parts":[[2022,12,23]],"date-time":"2022-12-23T04:24:53Z","timestamp":1671769493000},"page":"48","update-policy":"https:\/\/doi.org\/10.3390\/mdpi_crossmark_policy","source":"Crossref","is-referenced-by-count":13,"title":["Targeting OPA1-Mediated Mitochondrial Fusion Contributed to Celastrol\u2019s Anti-Tumor Angiogenesis Effect"],"prefix":"10.3390","volume":"15","author":[{"given":"Gaofu","family":"Li","sequence":"first","affiliation":[{"name":"Department of Pharmaceutical Sciences, Beijing Institute of Radiation Medicine, Beijing 100850, China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Lei","family":"Zhou","sequence":"additional","affiliation":[{"name":"School of Pharmacy, Guangdong Pharmaceutical University, Guangzhou 510006, China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Huifang","family":"Deng","sequence":"additional","affiliation":[{"name":"Department of Pharmaceutical Sciences, Beijing Institute of Radiation Medicine, Beijing 100850, China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Congshu","family":"Huang","sequence":"additional","affiliation":[{"name":"School of Chinese Materia Medica, Tianjin University of Traditional Chinese Medicine, Tianjin 301617, China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Ningning","family":"Wang","sequence":"additional","affiliation":[{"name":"Department of Pharmaceutical Sciences, Beijing Institute of Radiation Medicine, Beijing 100850, China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Lanxin","family":"Yue","sequence":"additional","affiliation":[{"name":"Department of Pharmaceutical Sciences, Beijing Institute of Radiation Medicine, Beijing 100850, China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Pengfei","family":"Zhang","sequence":"additional","affiliation":[{"name":"Department of Pharmaceutical Sciences, Beijing Institute of Radiation Medicine, Beijing 100850, China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Yongqiang","family":"Zhou","sequence":"additional","affiliation":[{"name":"Department of Pharmaceutical Sciences, Beijing Institute of Radiation Medicine, Beijing 100850, China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-0435-7261","authenticated-orcid":false,"given":"Wei","family":"Zhou","sequence":"additional","affiliation":[{"name":"Department of Pharmaceutical Sciences, Beijing Institute of Radiation Medicine, Beijing 100850, China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Yue","family":"Gao","sequence":"additional","affiliation":[{"name":"Department of Pharmaceutical Sciences, Beijing Institute of Radiation Medicine, Beijing 100850, China"},{"name":"School of Pharmacy, Guangdong Pharmaceutical University, Guangzhou 510006, China"},{"name":"School of Chinese Materia Medica, Tianjin University of Traditional Chinese Medicine, Tianjin 301617, China"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"1968","published-online":{"date-parts":[[2022,12,23]]},"reference":[{"key":"ref_1","doi-asserted-by":"crossref","first-page":"471","DOI":"10.1038\/s41598-019-57312-y","article-title":"Metabolomics reveals that cysteine metabolism plays a role in celastrol-induced mitochondrial apoptosis in hl-60 and nb-4 cells","volume":"10","author":"Chen","year":"2020","journal-title":"Sci. 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