{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,5,13]],"date-time":"2026-05-13T03:55:19Z","timestamp":1778644519149,"version":"3.51.4"},"reference-count":46,"publisher":"MDPI AG","issue":"6","license":[{"start":{"date-parts":[[2026,3,12]],"date-time":"2026-03-12T00:00:00Z","timestamp":1773273600000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"funder":[{"DOI":"10.13039\/501100004735","name":"Hunan Provincial Natural Science Foundation","doi-asserted-by":"publisher","award":["2023JJ40494"],"award-info":[{"award-number":["2023JJ40494"]}],"id":[{"id":"10.13039\/501100004735","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/501100004735","name":"Hunan Provincial Natural Science Foundation","doi-asserted-by":"publisher","award":["2024JJ8216"],"award-info":[{"award-number":["2024JJ8216"]}],"id":[{"id":"10.13039\/501100004735","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/501100004735","name":"Hunan Provincial Natural Science Foundation","doi-asserted-by":"publisher","award":["2026JJ80156"],"award-info":[{"award-number":["2026JJ80156"]}],"id":[{"id":"10.13039\/501100004735","id-type":"DOI","asserted-by":"publisher"}]}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":["Molecules"],"abstract":"<jats:p>Breast cancer represents a persistent global health burden, marked by extensive molecular heterogeneity and frequent therapeutic resistance in aggressive subtypes, particularly triple-negative breast cancer (TNBC). These clinical challenges underscore the urgency for alternative therapeutic strategies. Bioactive alkaloids isolated from Nelumbo nucifera, especially the bisbenzylisoquinoline compounds liensinine (LIE), isoliensinine (ISO), and neferine (NEF), have emerged as promising candidates due to their ability to disrupt oncogenic signaling pathways and inhibit malignant cellular transformation. The present study conducted a systematic investigation of LIE, ISO, and NEF across multiple breast cancer cell lines, including highly aggressive TNBC models. Results revealed potent growth-inhibitory effects mediated through apoptosis induction and cell cycle arrest at both the G1 and G2\/M phases. Furthermore, transcriptomic profiling and molecular analysis identified LIE as a principal effector, driving extensive transcriptional reprogramming and targeting the MAPK and mTOR pathways as core regulators of its anti-cancer efficacy. Collectively, these findings define a mechanistic framework for the anti-cancer potential of N. nucifera-derived alkaloids and provide a compelling foundation for their development as therapeutic candidates for advanced breast cancer.<\/jats:p>","DOI":"10.3390\/molecules31060947","type":"journal-article","created":{"date-parts":[[2026,3,12]],"date-time":"2026-03-12T14:46:31Z","timestamp":1773326791000},"page":"947","update-policy":"https:\/\/doi.org\/10.3390\/mdpi_crossmark_policy","source":"Crossref","is-referenced-by-count":1,"title":["Molecular Mechanisms Underlying the Anti-Tumor Activity of Lotus-Derived Alkaloids in Breast Cancer"],"prefix":"10.3390","volume":"31","author":[{"given":"Qinyi","family":"He","sequence":"first","affiliation":[{"name":"National & Local Joint Engineering Laboratory of Animal Peptide Drug Development, Peptide and Small Molecule Drug R&D Platform of Furong Laboratory, College of Life Sciences, Hunan Normal University, Changsha 410081, China"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Ling","family":"Luo","sequence":"additional","affiliation":[{"name":"National & Local Joint Engineering Laboratory of Animal Peptide Drug Development, Peptide and Small Molecule Drug R&D Platform of Furong Laboratory, College of Life Sciences, Hunan Normal University, Changsha 410081, China"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Dezhao","family":"Zhang","sequence":"additional","affiliation":[{"name":"National & Local Joint Engineering Laboratory of Animal Peptide Drug Development, Peptide and Small Molecule Drug R&D Platform of Furong Laboratory, College of Life Sciences, Hunan Normal University, Changsha 410081, China"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Wenxiang","family":"Zhou","sequence":"additional","affiliation":[{"name":"Hunan Engineering Research Center of Lotus Deep Processing and Nutritional Health Sciences, School of Life and Health Sciences, Hunan University of Science and Technology, Xiangtan 411201, China"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Ningning","family":"Bai","sequence":"additional","affiliation":[{"name":"Hunan Engineering Research Center of Lotus Deep Processing and Nutritional Health Sciences, School of Life and Health Sciences, Hunan University of Science and Technology, Xiangtan 411201, China"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-4722-9403","authenticated-orcid":false,"given":"Canwei","family":"Du","sequence":"additional","affiliation":[{"name":"Hunan Engineering Research Center of Lotus Deep Processing and Nutritional Health Sciences, School of Life and Health Sciences, Hunan University of Science and Technology, Xiangtan 411201, China"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Songlian","family":"Li","sequence":"additional","affiliation":[{"name":"Department of Breast Surgery, Second Affiliated Hospital of Hunan University of Chinese Medicine, Changsha 410036, China"}],"role":[{"role":"author","vocabulary":"crossref"}]}],"member":"1968","published-online":{"date-parts":[[2026,3,12]]},"reference":[{"key":"ref_1","first-page":"209","article-title":"Global Cancer Statistics 2020: GLOBOCAN Estimates of Incidence and Mortality Worldwide for 36 Cancers in 185 Countries","volume":"71","author":"Sung","year":"2021","journal-title":"CA Cancer J. 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