{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,1,12]],"date-time":"2026-01-12T23:13:28Z","timestamp":1768259608684,"version":"3.49.0"},"reference-count":61,"publisher":"MDPI AG","issue":"13","license":[{"start":{"date-parts":[[2025,6,27]],"date-time":"2025-06-27T00:00:00Z","timestamp":1750982400000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"funder":[{"DOI":"10.13039\/501100010034","name":"School of Engineering and Technology","doi-asserted-by":"publisher","award":["SETWU-2024-CPE-G22"],"award-info":[{"award-number":["SETWU-2024-CPE-G22"]}],"id":[{"id":"10.13039\/501100010034","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/501100010034","name":"School of Engineering and Technology","doi-asserted-by":"publisher","award":["WU-IRG-66247"],"award-info":[{"award-number":["WU-IRG-66247"]}],"id":[{"id":"10.13039\/501100010034","id-type":"DOI","asserted-by":"publisher"}]},{"name":"Walailak University","award":["SETWU-2024-CPE-G22"],"award-info":[{"award-number":["SETWU-2024-CPE-G22"]}]},{"name":"Walailak University","award":["WU-IRG-66247"],"award-info":[{"award-number":["WU-IRG-66247"]}]}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":["Molecules"],"abstract":"<jats:p>Lung cancer is a leading cause of cancer-related deaths globally, with current treatments having significant limitations, including drug resistance, metastasis, and tumor heterogeneity. This study investigated the anticancer potential of isalpinin, a flavonoid isolated from Paphiopedilum\u00a0dianthum, against non-small cell lung cancer (NSCLC) cell lines A549, H23, and H460. Isalpinin significantly inhibited NSCLC cell viability in a dose- and time-dependent manner; H23 and H460 cells showed greater sensitivity (IC50 a ~ 44 \u03bcM at 48 h) compared to A549 cells (IC50 82 \u03bcM). Isalpinin suppressed proliferation, migration, and anchorage-independent growth, particularly in H23\/H460 cells. Mechanistically, it induced apoptosis via increased ROS production and Bcl-2 downregulation, particularly in H23 and H460 cells. In a molecular docking analysis, isalpinin was found to directly bind to the ATP-binding pocket of AKT1, as confirmed by reduced Akt\/GSK3\u03b2 phosphorylation. These results suggest that isalpinin showed a potent multi-target natural compound against NSCLC that disrupts the key hallmarks of malignancy and pro-survival signaling. However, its subtype-specific efficacy warrants further in vivo studies and an investigation of combinatorial therapeutic approaches to elucidate its clinical potential.<\/jats:p>","DOI":"10.3390\/molecules30132762","type":"journal-article","created":{"date-parts":[[2025,6,27]],"date-time":"2025-06-27T05:29:58Z","timestamp":1751002198000},"page":"2762","update-policy":"https:\/\/doi.org\/10.3390\/mdpi_crossmark_policy","source":"Crossref","is-referenced-by-count":1,"title":["Antitumor Activity of Isalpinin from Paphiopedilum\u00a0dianthum on Non-Small Cell Lung Cancer Cell Lines"],"prefix":"10.3390","volume":"30","author":[{"given":"Phisit","family":"Pouyfung","sequence":"first","affiliation":[{"name":"Department of Occupational Health and Safety, School of Public Health, Walailak University, Nakhon Si Thammarat 80160, Thailand"},{"name":"Biomass and Oil Palm Center of Excellence, Walailak University, Nakhon Si Thammarat 80160, Thailand"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Nonthalert","family":"Lertnitikul","sequence":"additional","affiliation":[{"name":"Department of Pharmacognosy and Pharmaceutical Botany, Faculty of Pharmaceutical Sciences, Chulalongkorn University, Bangkok 10330, Thailand"},{"name":"Animal Models of Chronic Inflammation-Associated Diseases for Drug Discovery Research Unit, Chulalongkorn University, Bangkok 10330, Thailand"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-2683-4575","authenticated-orcid":false,"given":"Hua","family":"Bai","sequence":"additional","affiliation":[{"name":"College of Public Health, Kunming Medical University, Kunming 650500, China"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"ORCID":"https:\/\/orcid.org\/0009-0006-2942-3738","authenticated-orcid":false,"given":"Achitphol","family":"Chookaew","sequence":"additional","affiliation":[{"name":"Division of Hematopoiesis, Joint Research Center for Human Retrovirus Infection and Graduate School of Medical Sciences, Kumamoto University, Honjo, Chuou-ku, Kumamoto 860-0811, Japan"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-2220-0842","authenticated-orcid":false,"given":"Varisa","family":"Pongrakhananon","sequence":"additional","affiliation":[{"name":"Department of Pharmacology and Physiology, Faculty of Pharmaceutical Sciences, Chulalongkorn University, Bangkok 10330, Thailand"},{"name":"Center of Excellence in Preclinical Toxicity and Efficacy Assessment of Medicines and Chemicals, Chulalongkorn University, Bangkok 10330, Thailand"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-4707-3456","authenticated-orcid":false,"given":"Piriya","family":"Chonsut","sequence":"additional","affiliation":[{"name":"Department of Applied Thai Traditional Medicine, School of Medicine, Walailak University, Nakhon Si Tammarat 80160, Thailand"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-3233-0111","authenticated-orcid":false,"given":"Suwichak","family":"Chaisit","sequence":"additional","affiliation":[{"name":"Biomass and Oil Palm Center of Excellence, Walailak University, Nakhon Si Thammarat 80160, Thailand"},{"name":"Department of Chemical Engineering and Pharmaceutical Chemistry, School of Engineering and Technology, Walailak University, Nakhon Si Thammarat 80160, Thailand"}],"role":[{"role":"author","vocabulary":"crossref"}]}],"member":"1968","published-online":{"date-parts":[[2025,6,27]]},"reference":[{"key":"ref_1","doi-asserted-by":"crossref","first-page":"1583","DOI":"10.1097\/CM9.0000000000002529","article-title":"Global Burden and Trends of Lung Cancer Incidence and Mortality","volume":"136","author":"Li","year":"2023","journal-title":"Chin. 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