{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,8,18]],"date-time":"2026-08-18T04:49:36Z","timestamp":1787028576610,"version":"build-2736575974"},"reference-count":62,"publisher":"MDPI AG","issue":"2","license":[{"start":{"date-parts":[[2026,1,10]],"date-time":"2026-01-10T00:00:00Z","timestamp":1768003200000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"funder":[{"name":"School of Engineering and Technology","award":["SETWU-2024-CPE-G23"],"award-info":[{"award-number":["SETWU-2024-CPE-G23"]}]}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":["IJMS"],"abstract":"<jats:p>Lung cancer remains a major clinical challenge, with therapy resistance in non-small-cell lung cancer (NSCLC) driving the search for novel selective agents. This study demonstrates that 2,3\u2032-dihydroxy-5\u2032-methoxystilbene exhibits significant anticancer activity in NSCLC cell lines (A549, H23, and H460) while displaying substantially lower toxicity toward normal NIH\/3T3 fibroblasts. The compound reduced the viability of H23 and H460 cells after 48 h. (IC50: 23.39 \u00b1 3.27 \u03bcM and 24.20 \u00b1 2.61 \u03bcM, respectively), with NIH\/3T3 cells remaining comparatively resistant (IC50 &gt; 100 \u03bcM). At 25 \u03bcM, it suppressed proliferation by approximately 40% in H23, 30% in H460, and 20% in A549 cells, and dose-dependently impaired colony formation and migration, leading to near-complete migration arrest in H460 cells. Apoptosis induction peaked at 19% in H23, 17% in H460, and 8% in A549 cells at 25 \u03bcM. Mechanistic studies and molecular modeling revealed AKT-dependent activity, with decreased p-AKT and p-GSK3\u03b2 levels (0.70 and 0.75 in H23; 0.65 and 0.70 in H460 at 25 \u03bcM), without changes in total protein expression. Combination treatment with cisplatin yielded synergistic effects in A549 (CI = 0.83) and H460 (CI = 0.94) cells, but antagonistic effects in H23 cells (CI = 1.32). These findings identify 2,3\u2032-dihydroxy-5\u2032-methoxystilbene as a selective AKT-targeting stilbene with promising anticancer potential and context-dependent chemosensitizing activity in NSCLC cells.<\/jats:p>","DOI":"10.3390\/ijms27020719","type":"journal-article","created":{"date-parts":[[2026,1,12]],"date-time":"2026-01-12T09:13:01Z","timestamp":1768209181000},"page":"719","update-policy":"https:\/\/doi.org\/10.3390\/mdpi_crossmark_policy","source":"Crossref","is-referenced-by-count":1,"title":["Anticancer Activity of 2,3\u2032-Dihydroxy-5\u2032-Methoxystilbene Against NSCLC Cell Lines Through AKT-Dependent Mechanisms: A Comprehensive In Vitro and Computational Analysis"],"prefix":"10.3390","volume":"27","author":[{"ORCID":"https:\/\/orcid.org\/0000-0002-9825-2913","authenticated-orcid":false,"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":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-2365-1987","authenticated-orcid":false,"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":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-1877-7577","authenticated-orcid":false,"given":"Noriyoshi","family":"Ogino","sequence":"additional","affiliation":[{"name":"Third Department of Internal Medicine, School of Medicine, University of Occupational and Environmental Health, Iseigaoka 1-1, Yahatanishi-ku, Kitakyushu 807-8555, Japan"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"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, Graduate School of Medical Sciences, Kumamoto University, Honjo, Chuou-ku, Kumamoto 860-0811, Japan"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"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":[{"vocabulary":"crossref","role":"author"}]},{"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":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0009-0005-7521-4999","authenticated-orcid":false,"given":"Natthaporn","family":"Sueangoen","sequence":"additional","affiliation":[{"name":"Research Laboratory Section, Offices of Health Science Research, Faculty of Medicine Ramathibodi Hospital, Mahidol University, Bangkok 10400, Thailand"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"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":[{"vocabulary":"crossref","role":"author"}]}],"member":"1968","published-online":{"date-parts":[[2026,1,10]]},"reference":[{"key":"ref_1","unstructured":"World Health Organization (2025, November 23). 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