{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2025,10,3]],"date-time":"2025-10-03T12:43:28Z","timestamp":1759495408854,"version":"build-2065373602"},"reference-count":49,"publisher":"MDPI AG","issue":"10","license":[{"start":{"date-parts":[[2025,10,3]],"date-time":"2025-10-03T00:00:00Z","timestamp":1759449600000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"funder":[{"name":"Fundamental Fund of Khon Kaen University"},{"name":"Post Doctoral Training Program for Frontier Research from Khon Kaen University, Thailand","award":["PD2568-08"],"award-info":[{"award-number":["PD2568-08"]}]},{"name":"Center of Excellence for Innovation in Chemistry, Ministry of Higher Education, Science, Research and Innovation, Thailand"}],"content-domain":{"domain":["www.mdpi.com"],"crossmark-restriction":true},"short-container-title":["Biomolecules"],"abstract":"<jats:p>Lung cancer is a leading cause of cancer mortality worldwide. Targeted therapies with epidermal growth factor receptor (EGFR) tyrosine kinase inhibitors (TKIs) represent a significant advance in the management of lung cancer. However, their long-term efficacy is often limited by acquired resistance, particularly due to the T790M mutation, highlighting the need for novel EGFR-TKIs. Although compounds derived from Centella asiatica have demonstrated anticancer potential, their role in EGFR inhibition has not yet been reported. In this study, we investigated the inhibitory activity of two primary constituents, asiaticoside and asiatic acid, against wild-type and double-mutant (L858R\/T790M) EGFR, as well as the anticancer effects of the more potent compound in lung cancer cells. A kinase activity assay revealed that asiatic acid potently inhibited both wild-type and double-mutant EGFR, whereas asiaticoside showed minimal inhibitory activity. Molecular docking demonstrated that asiatic acid bound to the ATP-binding pocket of both EGFR forms with binding energies superior to those of erlotinib and osimertinib. Treatment with asiatic acid significantly (i) reduced viability of A549 and H1975 cells while remaining non-toxic to BEAS-2B normal lung cells, (ii) enhanced cancer cell apoptosis, (iii) suppressed extracellular signal-regulated kinase (ERK) and protein kinase B (Akt) signaling pathways, and (iv) inhibited EGFR activation in A549 and H1975 cells. These results suggest that asiatic acid is a promising lead compound for anticancer drug development.<\/jats:p>","DOI":"10.3390\/biom15101410","type":"journal-article","created":{"date-parts":[[2025,10,3]],"date-time":"2025-10-03T11:53:37Z","timestamp":1759492417000},"page":"1410","update-policy":"https:\/\/doi.org\/10.3390\/mdpi_crossmark_policy","source":"Crossref","is-referenced-by-count":0,"title":["Asiatic Acid from Centella asiatica as a Potent EGFR Tyrosine Kinase Inhibitor with Anticancer Activity in NSCLC Cells Harboring Wild-Type and T790M-Mutated EGFR"],"prefix":"10.3390","volume":"15","author":[{"ORCID":"https:\/\/orcid.org\/0000-0002-9267-3047","authenticated-orcid":false,"given":"Chaiwat","family":"Monmai","sequence":"first","affiliation":[{"name":"Department of Biochemistry, and Center for Translational Medicine, Faculty of Medicine, Khon Kaen University, Khon Kaen 40002, Thailand"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"ORCID":"https:\/\/orcid.org\/0009-0001-3390-8838","authenticated-orcid":false,"given":"Sahachai","family":"Sabuakham","sequence":"additional","affiliation":[{"name":"School of Biomolecular Science and Engineering, Vidyasirimedhi Institute of Science and Technology, Rayong 21210, Thailand"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-6445-7550","authenticated-orcid":false,"given":"Wachirachai","family":"Pabuprapap","sequence":"additional","affiliation":[{"name":"Department of Chemistry, and Center of Excellence for Innovation in Chemistry, Faculty of Science, Ramkhamhaeng University, Bangkok 10240, Thailand"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-6359-5828","authenticated-orcid":false,"given":"Waraluck","family":"Chaichompoo","sequence":"additional","affiliation":[{"name":"Department of Chemistry, and Center of Excellence for Innovation in Chemistry, Faculty of Science, Ramkhamhaeng University, Bangkok 10240, Thailand"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-8919-3555","authenticated-orcid":false,"given":"Apichart","family":"Suksamrarn","sequence":"additional","affiliation":[{"name":"Department of Chemistry, and Center of Excellence for Innovation in Chemistry, Faculty of Science, Ramkhamhaeng University, Bangkok 10240, Thailand"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-4389-334X","authenticated-orcid":false,"given":"Panupong","family":"Mahalapbutr","sequence":"additional","affiliation":[{"name":"Department of Biochemistry, and Center for Translational Medicine, Faculty of Medicine, Khon Kaen University, Khon Kaen 40002, Thailand"}],"role":[{"role":"author","vocabulary":"crossref"}]}],"member":"1968","published-online":{"date-parts":[[2025,10,3]]},"reference":[{"key":"ref_1","doi-asserted-by":"crossref","first-page":"104141","DOI":"10.1016\/j.critrevonc.2023.104141","article-title":"Bacteria-driven cancer therapy: Exploring advancements and challenges","volume":"191","author":"Din","year":"2023","journal-title":"Crit. 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