{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,9,12]],"date-time":"2026-09-12T06:15:03Z","timestamp":1789193703707,"version":"build-2803163510"},"reference-count":53,"publisher":"MDPI AG","issue":"17","license":[{"start":{"date-parts":[[2024,8,25]],"date-time":"2024-08-25T00:00:00Z","timestamp":1724544000000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"funder":[{"name":"Natural Science Funding of Shanxi Province","award":["202203021221010"],"award-info":[{"award-number":["202203021221010"]}]},{"name":"Natural Science Funding of Shanxi Province","award":["202104010910001"],"award-info":[{"award-number":["202104010910001"]}]},{"name":"Shanxi Key Laboratory of Redevelopment of Famous Local Traditional Chinese Medicines, Shanxi University","award":["202203021221010"],"award-info":[{"award-number":["202203021221010"]}]},{"name":"Shanxi Key Laboratory of Redevelopment of Famous Local Traditional Chinese Medicines, Shanxi University","award":["202104010910001"],"award-info":[{"award-number":["202104010910001"]}]}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":["IJMS"],"abstract":"<jats:p>Intrahepatic cholangiocarcinoma (ICC) is a universally lethal malignancy with increasing incidence. However, ICC patients receive limited benefits from current drugs; therefore, we must urgently explore new drugs for treating ICC. Quinolizidine alkaloids, as essential active ingredients extracted from Sophora alopecuroides Linn, can suppress cancer cell growth via numerous mechanisms and have therapeutic effects on liver-related diseases. However, the impact of quinolizidine alkaloids on intrahepatic cholangiocarcinoma has not been fully studied. In this article, the in vitro anti-ICC activities of six natural quinolizidine alkaloids were explored. Aloperine was the most potent antitumor compound among the tested quinolizidine alkaloids, and it preferentially inhibited RBE cells rather than HCCC-9810 cells. Mechanistically, aloperine can potentially decrease glutamate content by inhibiting the hydrolysis of glutamine, reducing D-2-hydroxyglutarate levels and, consequently, leading to preferential growth inhibition in isocitrate dehydrogenase (IDH)-mutant ICC cells. In addition, aloperine preferentially resensitizes RBE cells to 5-fluorouracil, AGI-5198 and olaparib. This article demonstrates that aloperine shows preferential antitumor effects in intrahepatic cholangiocarcinoma cells harboring the mutant IDH1 by decreasing D-2-hydroxyglutarate, suggesting that aloperine could be used as a lead compound or adjuvant chemotherapy drug to treat ICC harboring the mutant IDH.<\/jats:p>","DOI":"10.3390\/ijms25179226","type":"journal-article","created":{"date-parts":[[2024,8,26]],"date-time":"2024-08-26T07:53:37Z","timestamp":1724658817000},"page":"9226","update-policy":"https:\/\/doi.org\/10.3390\/mdpi_crossmark_policy","source":"Crossref","is-referenced-by-count":4,"title":["Discovery of Aloperine as a Potential Antineoplastic Agent for Cholangiocarcinoma Harboring Mutant IDH1"],"prefix":"10.3390","volume":"25","author":[{"ORCID":"https:\/\/orcid.org\/0000-0001-6480-7952","authenticated-orcid":false,"given":"Xingkang","family":"Wu","sequence":"first","affiliation":[{"name":"Modern Research Center for Traditional Chinese Medicine, Key Laboratory of Chemical Biology and Molecular Engineering of Ministry of Education, Shanxi University, No. 92, Wucheng Road, Taiyuan 030006, China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Yang","family":"Li","sequence":"additional","affiliation":[{"name":"Modern Research Center for Traditional Chinese Medicine, Key Laboratory of Chemical Biology and Molecular Engineering of Ministry of Education, Shanxi University, No. 92, Wucheng Road, Taiyuan 030006, China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Chenchen","family":"Han","sequence":"additional","affiliation":[{"name":"Modern Research Center for Traditional Chinese Medicine, Key Laboratory of Chemical Biology and Molecular Engineering of Ministry of Education, Shanxi University, No. 92, Wucheng Road, Taiyuan 030006, China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-2112-585X","authenticated-orcid":false,"given":"Shifei","family":"Li","sequence":"additional","affiliation":[{"name":"Key Laboratory of Chemical Biology and Molecular Engineering of Education Ministry, Institute of Molecular Science, Shanxi University, No. 92, Wucheng Road, Taiyuan 030006, China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Xuemei","family":"Qin","sequence":"additional","affiliation":[{"name":"Modern Research Center for Traditional Chinese Medicine, Key Laboratory of Chemical Biology and Molecular Engineering of Ministry of Education, Shanxi University, No. 92, Wucheng Road, Taiyuan 030006, China"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"1968","published-online":{"date-parts":[[2024,8,25]]},"reference":[{"key":"ref_1","doi-asserted-by":"crossref","first-page":"198","DOI":"10.3322\/caac.21759","article-title":"Advances in the treatment of intrahepatic cholangiocarcinoma: An overview of the current and future therapeutic landscape for clinicians","volume":"73","author":"Moris","year":"2022","journal-title":"CA-Cancer J. 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