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Natural products are important and sustainable sources of new anticancer drug molecules, offering new bioactive molecules with various structures and biofunctions for new anticancer drug development, which accounted for 40% of all anticancer drugs. Natural-based compounds could inhibit cancer cell proliferation and migration through a variety of anticancer mechanisms by the modulation\/regulation of multiple biotargets and cell signaling pathways. In this review, we summarized the anticancer activities of flavonoids, terpenoids, glycosides, alcohols, coumarins, saccharides, and other natural compounds that could modulate the ERK-related signaling pathway in non-small-cell lung cancer (NSCLC) cells. We further elucidated the mechanistic pathways of natural compound combinations and computationally predicted their molecular docking affinities with ERK1\/ERK2 protein targets, as well as providing an outlook on current studies, with the expectation that natural compounds will play more significant roles in future antitumor chemotherapy regimens.<\/jats:p>","DOI":"10.3390\/ph18091371","type":"journal-article","created":{"date-parts":[[2025,9,15]],"date-time":"2025-09-15T07:56:51Z","timestamp":1757923011000},"page":"1371","update-policy":"https:\/\/doi.org\/10.3390\/mdpi_crossmark_policy","source":"Crossref","is-referenced-by-count":3,"title":["Progress of ERK Pathway-Modulated Natural Products for Anti-Non-Small-Cell Lung Cancer Activity"],"prefix":"10.3390","volume":"18","author":[{"given":"Lin","family":"Xing","sequence":"first","affiliation":[{"name":"College of Food Science and Technology, Shanghai Ocean University, Shanghai 201306, China"}]},{"given":"Chi","family":"Zhang","sequence":"additional","affiliation":[{"name":"College of Food Science and Technology, Shanghai Ocean University, Shanghai 201306, China"}]},{"given":"Jieying","family":"Yuan","sequence":"additional","affiliation":[{"name":"College of Food Science and Technology, Shanghai Ocean University, Shanghai 201306, China"}]},{"given":"Kai","family":"Zhu","sequence":"additional","affiliation":[{"name":"College of Food Science and Technology, Shanghai Ocean University, Shanghai 201306, China"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-7856-2041","authenticated-orcid":false,"given":"Helena","family":"Tom\u00e1s","sequence":"additional","affiliation":[{"name":"CQM\u2014Centro de Qu\u00edmica da Madeira, Universidade da Madeira, Campus da Penteada, 9000-390 Funchal, Portugal"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-3303-3832","authenticated-orcid":false,"given":"Ruilong","family":"Sheng","sequence":"additional","affiliation":[{"name":"CQM\u2014Centro de Qu\u00edmica da Madeira, Universidade da Madeira, Campus da Penteada, 9000-390 Funchal, Portugal"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-5591-6951","authenticated-orcid":false,"given":"Xiuwei H.","family":"Yang","sequence":"additional","affiliation":[{"name":"Department of Pharmacology and Nutritional Sciences, University of Kentucky, Lexington, KY 40506-0107, USA"}]},{"given":"Qidong","family":"Tu","sequence":"additional","affiliation":[{"name":"Jiangxi Provincial Key Laboratory of Drug Design and Evaluation, School of Pharmacy, Jiangxi Science & Technology Normal University, Nanchang 330013, China"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-8414-886X","authenticated-orcid":false,"given":"Ruihua","family":"Guo","sequence":"additional","affiliation":[{"name":"College of Food Science and Technology, Shanghai Ocean University, Shanghai 201306, China"},{"name":"Department of Marine Biopharmacology, College of Food Science and Technology, Shanghai Ocean University, Shanghai 201306, China"},{"name":"Marine Biomedical Science and Technology Innovation Platform of Lin-gang Special Area, Shanghai 201306, China"}]}],"member":"1968","published-online":{"date-parts":[[2025,9,12]]},"reference":[{"key":"ref_1","doi-asserted-by":"crossref","first-page":"106160","DOI":"10.1016\/j.phrs.2022.106160","article-title":"Wang, Therapeutic targeting ROR\u03b3 with natural product N-hydroxyapiosporamide for small cell lung cancer by reprogramming neuroendocrine fate","volume":"178","author":"Chen","year":"2022","journal-title":"Pharmacol. Res."},{"key":"ref_2","doi-asserted-by":"crossref","first-page":"45","DOI":"10.1016\/j.phytol.2022.02.013","article-title":"Curcumin: A potential therapeutic natural product for adenocarcinomas","volume":"49","author":"Nasery","year":"2022","journal-title":"Phytochem. Lett."},{"key":"ref_3","doi-asserted-by":"crossref","first-page":"191","DOI":"10.1007\/s43441-022-00375-3","article-title":"Anti-lung Cancer Marine Compounds: A Review","volume":"56","author":"Miri","year":"2022","journal-title":"Ther. Innov. Regul. Sci."},{"key":"ref_4","first-page":"1447","article-title":"Natural compounds for cancer treatment and prevention","volume":"77","author":"Nobili","year":"2009","journal-title":"Pharmacol. Res."},{"key":"ref_5","first-page":"365","article-title":"Ready for a comeback of natural products in oncology","volume":"59","author":"Bailly","year":"2009","journal-title":"Biochem. Pharmacol."},{"key":"ref_6","doi-asserted-by":"crossref","first-page":"105504","DOI":"10.1016\/j.fitote.2023.105504","article-title":"Synthesis and biological evaluation of novel demethylzeylasteral derivatives as potential anticancer agents","volume":"167","author":"Sun","year":"2023","journal-title":"Fitoterapia"},{"key":"ref_7","first-page":"1088","article-title":"Effects of cordycepin on the growth and migration of lung cancer cells","volume":"41","author":"Song","year":"2022","journal-title":"Mycosystema"},{"key":"ref_8","doi-asserted-by":"crossref","first-page":"1346","DOI":"10.7150\/jca.67513","article-title":"RPS9 promotes the progression of NSCLC via activation Stat3 and Erk signaling pathways","volume":"13","author":"Kong","year":"2022","journal-title":"J. Cancer"},{"key":"ref_9","doi-asserted-by":"crossref","first-page":"1536","DOI":"10.7150\/ijbs.40042","article-title":"Bisdemethoxycurcumin enhances the sensitivity of non-small cell Lung cancer cells to Icotinib via dual induction of autophagy and apoptosis","volume":"16","author":"Xiang","year":"2020","journal-title":"Int. J. Biol. Sci."},{"key":"ref_10","first-page":"871","article-title":"The mechanism of antitumor natural products targeting on MAPK signal pathway","volume":"30","author":"Yu","year":"2010","journal-title":"Chem. Life"},{"key":"ref_11","doi-asserted-by":"crossref","unstructured":"Sankaranarayanan, R., Kumar, D.R., Patel, J., and Bhat, G.J. (2020). Do Aspirin and Flavonoids Prevent Cancer through a Common Mechanism Involving Hydroxybenzoic Acids?\u2014The Metabolite Hypothesis. Molecules, 25.","DOI":"10.3390\/molecules25092243"},{"key":"ref_12","doi-asserted-by":"crossref","unstructured":"Selvakumar, P., Badgeley, A., Murphy, P., Anwar, H., Sharma, U., Lawrence, K., and Lakshmikuttyamma, A. (2020). Flavonoids and Other Polyphenols Act as Epigenetic Modifiers in Breast Cancer. Nutrients, 12.","DOI":"10.3390\/nu12030761"},{"key":"ref_13","doi-asserted-by":"crossref","unstructured":"Izzo, S., Naponelli, V., and Bettuzzi, S. (2020). Flavonoids as Epigenetic Modulators for Prostate Cancer Prevention. Nutrients, 12.","DOI":"10.3390\/nu12041010"},{"key":"ref_14","doi-asserted-by":"crossref","first-page":"20220977","DOI":"10.1515\/biol-2022-0977","article-title":"Combination effect of flavonoids attenuates lung cancer cell proliferation by inhibiting the STAT3 and FAK signaling pathway","volume":"19","author":"Wan","year":"2024","journal-title":"Open Life Sci."},{"key":"ref_15","doi-asserted-by":"crossref","first-page":"182","DOI":"10.4077\/CJP.2014.BAC200","article-title":"Inhibitory Effects of Scutellarein on Proliferation of Human Lung Cancer A549 Cells through ERK and NF\u03baB Mediated by the EGFR Pathway","volume":"57","author":"Cheng","year":"2014","journal-title":"Chin. J. Physiol."},{"key":"ref_16","doi-asserted-by":"crossref","first-page":"1","DOI":"10.3389\/fphar.2018.00092","article-title":"Scutellarin Increases Cisplatin-Induced Apoptosis and Autophagy to Overcome Cisplatin Resistance in Non-small Cell Lung Cancer via ERK\/p53 and c-met\/AKT Signaling Pathways","volume":"9","author":"Sun","year":"2018","journal-title":"Front. Pharmacol."},{"key":"ref_17","doi-asserted-by":"crossref","unstructured":"Wang, J., Liu, X., Zheng, H., Liu, Q., Zhang, H., Wang, X., Shen, T., Wang, S., and Ren, D. (2020). Morusin induces apoptosis and autophagy via JNK, ERK and PI3K\/Akt signaling in human lung carcinoma cells. Chem. Biol. Interact., 331.","DOI":"10.1016\/j.cbi.2020.109279"},{"key":"ref_18","doi-asserted-by":"crossref","first-page":"2121","DOI":"10.1002\/mc.22456","article-title":"Oroxylin A inhibits invasion and migration through suppressing ERK\/GSK-3\u03b2 signaling in snail-expressing non-small-cell lung cancer cells","volume":"55","author":"Wei","year":"2016","journal-title":"Mol. Carcinog."},{"key":"ref_19","doi-asserted-by":"crossref","first-page":"1","DOI":"10.1155\/2020\/2491304","article-title":"Trifolium Flavonoids Overcome Gefitinib Resistance of Non-Small-Cell Lung Cancer Cell by Suppressing ERK and STAT3 Signaling Pathways","volume":"2020","author":"Wu","year":"2020","journal-title":"BioMed Res. Int."},{"key":"ref_20","doi-asserted-by":"crossref","first-page":"26","DOI":"10.1016\/j.cbi.2016.07.028","article-title":"Luteolin exerts pro-apoptotic effect and anti-migration effects on A549 lung adenocarcinoma cells through the activation of MEK\/ERK signaling pathway","volume":"257","author":"Meng","year":"2016","journal-title":"Chem. Biol. Interact."},{"key":"ref_21","first-page":"936","article-title":"In vitro and in vivo cytotoxic effects of chrysoeriol in human lung carcinoma are facilitated through activation of autophagy, sub-G1 cell cycle arrest, cell migration and invasion inhibition and modulation of MAPK\/ERK signaling pathway","volume":"24","author":"Wei","year":"2019","journal-title":"J. BUON"},{"key":"ref_22","doi-asserted-by":"crossref","first-page":"23436","DOI":"10.18632\/oncotarget.15584","article-title":"Parthenolide suppresses non-small cell lung cancer GLC-82 cells growth via B-Raf\/MAPK\/Erk pathway","volume":"8","author":"Lin","year":"2017","journal-title":"Oncotarget"},{"key":"ref_23","first-page":"1243","article-title":"Cbl-regulated Akt and ERK signals are involved in \u03b2-elemene-induced cell apoptosis in lung cancer cells","volume":"4","author":"Li","year":"2011","journal-title":"Mol. Med. Rep."},{"key":"ref_24","doi-asserted-by":"crossref","first-page":"2608","DOI":"10.3892\/ijo.2016.3488","article-title":"Oridonin inhibits gefitinib-resistant lung cancer cells by suppressing EGFR\/ERK\/MMP-12 and CIP2A\/Akt signaling pathways","volume":"48","author":"Xiao","year":"2016","journal-title":"Int. J. Oncol."},{"key":"ref_25","doi-asserted-by":"crossref","first-page":"2294","DOI":"10.3892\/ijo.2016.3727","article-title":"Kahweol induces apoptosis by suppressing BTF3 expression through the ERK signaling pathway in non-small cell lung cancer cells","volume":"49","author":"Jeon","year":"2016","journal-title":"Int. J. Oncol."},{"key":"ref_26","first-page":"248","article-title":"In vitro anticancer effects of levopimaric acid in cisplatin resistant human lung carcinoma are mediated via autophagy, ROS-mediated mitochondrial dysfunction, cell apoptosis and modulation of ERK\/MAPK\/JNK signalling pathway","volume":"25","author":"Zhang","year":"2020","journal-title":"J. BUON"},{"key":"ref_27","doi-asserted-by":"crossref","first-page":"2679","DOI":"10.1007\/s10886-006-9191-z","article-title":"Rapid Analysis of Abietanes in Conifers","volume":"32","author":"Kersten","year":"2006","journal-title":"J. Chem. Ecol."},{"key":"ref_28","doi-asserted-by":"crossref","first-page":"201","DOI":"10.2174\/1871520620666200424131548","article-title":"Anti-Metastatic Effects of Lupeol via the Inhibition of MAPK\/ERK Pathway in Lung Cancer","volume":"21","author":"Bhatt","year":"2020","journal-title":"Anti-Cancer Agents Med. Chem."},{"key":"ref_29","doi-asserted-by":"crossref","first-page":"145","DOI":"10.1007\/978-3-319-41342-6_7","article-title":"Lupeol and Its Role in Chronic Diseases","volume":"7","author":"Tsai","year":"2016","journal-title":"Drug Discov. Mother Nat."},{"key":"ref_30","doi-asserted-by":"crossref","first-page":"2009","DOI":"10.1002\/ptr.6132","article-title":"Toosendanin; a natural product, inhibited TGF-\u03b21-induced epithelial-mesenchymal transition through ERK\/Snail pathway","volume":"32","author":"Luo","year":"2018","journal-title":"Phytother. Res."},{"key":"ref_31","doi-asserted-by":"crossref","first-page":"753","DOI":"10.1142\/S0192415X2150035X","article-title":"20(S)-Ginsenoside Rg3 Inhibits Lung Cancer Cell Proliferation by Targeting EGFR-Mediated Ras\/Raf\/MEK\/ERK Pathway","volume":"49","author":"Liang","year":"2021","journal-title":"Am. J. Chin. Med."},{"key":"ref_32","doi-asserted-by":"crossref","first-page":"431","DOI":"10.1016\/j.bbrc.2018.02.188","article-title":"The inhibitory effect of Cordycepin on the proliferation of cisplatin-resistant A549 lung cancer cells","volume":"498","author":"Cho","year":"2018","journal-title":"Biochem. Biophys. Res. Commun."},{"key":"ref_33","doi-asserted-by":"crossref","first-page":"1319","DOI":"10.1111\/1759-7714.13019","article-title":"Hydroxysafflor yellow A inhibited lipopolysaccharide induced non-small cell lung cancer cell proliferation, migration, and invasion by suppressing the PI3K\/AKT\/mTOR and ERK\/MAPK signaling pathways","volume":"10","author":"Jiang","year":"2019","journal-title":"Thorac. Cancer"},{"key":"ref_34","doi-asserted-by":"crossref","first-page":"1141","DOI":"10.1016\/j.jep.2013.12.025","article-title":"Effects of hydroxysafflor yellow A on the activity and mRNA expression of four CYP isozymes in rats","volume":"151","author":"Xu","year":"2014","journal-title":"J. Ethnopharmacol."},{"key":"ref_35","doi-asserted-by":"crossref","first-page":"609","DOI":"10.1159\/000322328","article-title":"Periplocin Inhibits Growth of Lung Cancer in vitro and in vivo by Blocking AKT\/ERK Signaling Pathways","volume":"26","author":"Lu","year":"2010","journal-title":"Cell. Physiol. Biochem."},{"key":"ref_36","doi-asserted-by":"crossref","first-page":"11484","DOI":"10.3390\/molecules171011484","article-title":"The Antioxidant and Anti-inflammatory Effects of Phenolic Compounds Isolated from the Root of Rhodiola sachalinensis A. BOR","volume":"17","author":"Choe","year":"2012","journal-title":"Molecules"},{"key":"ref_37","doi-asserted-by":"crossref","first-page":"9","DOI":"10.1007\/s00011-012-0545-4","article-title":"Salidroside attenuates inflammatory responses by suppressing nuclear factor-jB and mitogen activated protein kinases activation in lipopolysaccharide-induced mastitis in mice","volume":"62","author":"Li","year":"2012","journal-title":"Inflamm. Res."},{"key":"ref_38","doi-asserted-by":"crossref","first-page":"37","DOI":"10.1002\/ptr.2013","article-title":"Adaptogenic and Central Nervous System Effects of Single Doses of 3% Rosavin and 1% Salidroside Rhodiola rosea L. Extract in Mice","volume":"21","author":"Perfumi","year":"2006","journal-title":"Phytother. Res."},{"key":"ref_39","doi-asserted-by":"crossref","first-page":"308","DOI":"10.1016\/j.jep.2010.09.025","article-title":"Salidroside promotes erythropoiesis and protects erythroblasts against oxidative stress by up-regulating glutathione peroxidase and thioredoxin","volume":"133","author":"Qian","year":"2011","journal-title":"J. Ethnopharmacol."},{"key":"ref_40","doi-asserted-by":"crossref","first-page":"1014","DOI":"10.1080\/21691401.2019.1584566","article-title":"Salidroside represses proliferation, migration and invasion of human lung cancer cells through AKT and MEK\/ERK signal pathway","volume":"47","author":"Ren","year":"2019","journal-title":"Artif. Cells Nanomed. Biotechnol."},{"key":"ref_41","doi-asserted-by":"crossref","first-page":"146","DOI":"10.1016\/j.phymed.2008.07.013","article-title":"The in vitro and in vivo antiviral effects of salidroside from Rhodiola rosea L. against coxsackievirus B3","volume":"16","author":"Wang","year":"2009","journal-title":"Phytomedicine"},{"key":"ref_42","doi-asserted-by":"crossref","first-page":"147","DOI":"10.3892\/mmr.2013.1468","article-title":"Salidroside protects against hydrogen peroxide-induced injury in HUVECs via the regulation of REDD1 and mTOR activation","volume":"8","author":"Xu","year":"2013","journal-title":"Mol. Med. Rep."},{"key":"ref_43","doi-asserted-by":"crossref","first-page":"3351268","DOI":"10.1155\/2022\/3351268","article-title":"Echinacoside Induces Mitochondria-Mediated Pyroptosis through Raf\/MEK\/ERK Signaling in Non-Small Cell Lung Cancer Cells","volume":"2022","author":"Shi","year":"2022","journal-title":"J. Immunol. Res."},{"key":"ref_44","doi-asserted-by":"crossref","first-page":"4703","DOI":"10.1021\/pr070399r","article-title":"Dioscin (Saponin)-Induced Generation of Reactive Oxygen Species through Mitochondria Dysfunction: A Proteomic-Based Study","volume":"6","author":"Wang","year":"2007","journal-title":"J. Proteome Res."},{"key":"ref_45","doi-asserted-by":"crossref","first-page":"1353","DOI":"10.1248\/cpb.52.1353","article-title":"A New Steroidal Saponin from Dioscorea cayenensis","volume":"52","author":"Sautour","year":"2004","journal-title":"Chem. Pharm. Bull."},{"key":"ref_46","doi-asserted-by":"crossref","first-page":"1927","DOI":"10.1007\/s00204-013-1047-z","article-title":"Dioscin-induced autophagy mitigates cell apoptosis through modulation of PI3K\/Akt and ERK and JNK signaling pathways in human lung cancer cell lines","volume":"87","author":"Hsieh","year":"2013","journal-title":"Arch. Toxicol."},{"key":"ref_47","doi-asserted-by":"crossref","first-page":"7670","DOI":"10.1016\/j.bmc.2009.09.046","article-title":"Structural analogues of diosgenyl saponins: Synthesis and anticancer activity","volume":"17","author":"Kaskiw","year":"2009","journal-title":"Bioorg. Med. Chem."},{"key":"ref_48","doi-asserted-by":"crossref","first-page":"407","DOI":"10.1055\/s-0030-1250461","article-title":"Application of Proteomic and Bioinformatic Techniques for Studying the Hepatoprotective Effect of Dioscin against CCl4-induced Liver Damage in Mice","volume":"77","author":"Lu","year":"2010","journal-title":"Planta Medica"},{"key":"ref_49","doi-asserted-by":"crossref","first-page":"363","DOI":"10.1016\/j.jchromb.2006.10.050","article-title":"Determination of protodioscin in rat plasma by liquid chromatography\u2013tandem mass spectrometry","volume":"848","author":"Wang","year":"2007","journal-title":"J. Chromatogr. B"},{"key":"ref_50","doi-asserted-by":"crossref","first-page":"3963","DOI":"10.1016\/j.bmcl.2016.07.004","article-title":"Timosaponin AIII inhibits migration and invasion of A549 human non-small-cell lung cancer cells via attenuations of MMP-2 and MMP-9 by inhibitions of ERK1\/2, Src\/FAK and b-catenin signaling pathways","volume":"26","author":"Jung","year":"2016","journal-title":"Bioorg. Med. Chem. Lett."},{"key":"ref_51","doi-asserted-by":"crossref","first-page":"760","DOI":"10.1016\/j.ejmech.2016.09.066","article-title":"Chemosensitizing effect of Paris Saponin I on Camptothecin and 10 hydroxycamptothecin in lung cancer cells via p38 MAPK, ERK, and Akt signaling pathways","volume":"125","author":"Liu","year":"2017","journal-title":"Eur. J. Med. Chem."},{"key":"ref_52","doi-asserted-by":"crossref","first-page":"1234","DOI":"10.1248\/bpb.28.1234","article-title":"Anti-inflammatory Activities of Aqueous Extract from Radix Ophiopogon japonicus and Its Two Constituents","volume":"28","author":"Kou","year":"2005","journal-title":"Biol. Pharm. Bull."},{"key":"ref_53","doi-asserted-by":"crossref","first-page":"1267","DOI":"10.1248\/bpb.29.1267","article-title":"Antithrombotic Activities of Aqueous Extract from Radix Ophiopogon japonicus and Its Two Constituents","volume":"29","author":"Kou","year":"2006","journal-title":"Biol. Pharm. Bull."},{"key":"ref_54","doi-asserted-by":"crossref","first-page":"1192","DOI":"10.1248\/bpb.33.1192","article-title":"The Saponin Monomer of Dwarf Lilyturf Tuber, DT-13, Reduces Human Breast Cancer Cell Adhesion and Migration during Hypoxia via Regulation of Tissue Factor","volume":"33","author":"Sun","year":"2010","journal-title":"Biol. Pharm. Bull."},{"key":"ref_55","doi-asserted-by":"crossref","first-page":"1277","DOI":"10.1016\/j.biopha.2017.02.104","article-title":"DT-13, a saponin monomer 13 of the Dwarf lilyturf tuber, synergized with vinorelbine to induce mitotic arrest via activation of ERK signaling pathway in NCI-H1299 cells","volume":"89","author":"Li","year":"2017","journal-title":"Biomed. Pharmacother."},{"key":"ref_56","doi-asserted-by":"crossref","first-page":"1121","DOI":"10.3892\/mmr.2012.1047","article-title":"DT-13 suppresses MDA-MB-435 cell adhesion and invasion by inhibiting MMP-2\/9 via the p38 MAPK pathway","volume":"6","author":"Zhang","year":"2012","journal-title":"Mol. Med. Rep."},{"key":"ref_57","doi-asserted-by":"crossref","first-page":"18600","DOI":"10.1002\/jcb.28696","article-title":"Theantitumoreffect of hinesol, extract from Atractylodes lancea (Thunb.) DC. byproliferation, inhibition, and apoptosis induction via MEK\/ERKandNF-\u03baBpathwayin non\u2013small cell lung cancer cell lines A549 and NCI-H1299","volume":"120","author":"Guo","year":"2019","journal-title":"J. Cell. Biochem."},{"key":"ref_58","doi-asserted-by":"crossref","first-page":"152809","DOI":"10.1016\/j.phymed.2018.12.032","article-title":"Fucosterol exerts antiproliferative effects on human lung cancer cells by inducing apoptosis, cell cycle arrest and targeting of Raf\/MEK\/ERK signalling pathway","volume":"61","author":"Mao","year":"2019","journal-title":"Phytomedicine"},{"key":"ref_59","doi-asserted-by":"crossref","first-page":"713","DOI":"10.1016\/0306-3623(95)02112-4","article-title":"Pharmacological and Biochemical Actions of Simple Coumarins: Natural Products with Therapeutic Potential","volume":"27","author":"Hoult","year":"1996","journal-title":"Gen. Pharmacol. Vasc. Syst."},{"key":"ref_60","doi-asserted-by":"crossref","first-page":"2875","DOI":"10.1016\/S0960-894X(99)00492-8","article-title":"Structure-activity Relationship in two series of Aminoalkyl Substituted Coumarin Inhibitors of Gyrase B","volume":"9","author":"Laurin","year":"1999","journal-title":"Bioorg. Med. Chem. Lett."},{"key":"ref_61","doi-asserted-by":"crossref","first-page":"47","DOI":"10.2174\/1568011053352622","article-title":"Chemical Aspects of Coumarin Compounds for the Prevention of Hepatocellular Carcinomas","volume":"5","author":"Okamoto","year":"2005","journal-title":"Anti-Cancer Agents Med. Chem."},{"key":"ref_62","doi-asserted-by":"crossref","first-page":"703","DOI":"10.1016\/j.cellbi.2005.04.003","article-title":"Effects of coumarin and 7OH-coumarin on bcl-2 and Bax expression in two human lung cancer cell lines in vitro","volume":"29","author":"Santos","year":"2005","journal-title":"Cell Biol. Int."},{"key":"ref_63","doi-asserted-by":"crossref","first-page":"2447","DOI":"10.1016\/j.febslet.2007.04.052","article-title":"7,8-Dihydroxy-4-methylcoumarin induces apoptosis of human lung adenocarcinoma cells by ROS-independent mitochondrial pathway through partial inhibition of ERK\/MAPK signaling","volume":"581","author":"Goel","year":"2007","journal-title":"FEBS Lett."},{"key":"ref_64","doi-asserted-by":"crossref","first-page":"275","DOI":"10.1016\/j.lungcan.2003.09.005","article-title":"Apoptosis and cell cycle disturbances induced by coumarin and 7-hydroxycoumarin on human lung carcinoma cell lines","volume":"43","author":"Mandoki","year":"2004","journal-title":"Lung Cancer"},{"key":"ref_65","doi-asserted-by":"crossref","first-page":"1638","DOI":"10.21037\/tcr-24-1771","article-title":"Scoparone suppresses proliferation and cell cycle of hepatocellular carcinoma cells via inhibiting AKT\/GSK-3\u03b2\/cyclin D1 signaling pathway","volume":"14","author":"Hong","year":"2025","journal-title":"Transl. Cancer Res."},{"key":"ref_66","doi-asserted-by":"crossref","first-page":"3504","DOI":"10.3892\/or.2016.5166","article-title":"Angelicin inhibits human lung carcinoma A549 cell growth and migration through regulating JNK and ERK pathways","volume":"36","author":"Li","year":"2016","journal-title":"Oncol. Rep."},{"key":"ref_67","doi-asserted-by":"crossref","first-page":"893","DOI":"10.1159\/000430264","article-title":"NBM-T-BMX-OS01, an Osthole Derivative, Sensitizes Human Lung Cancer A549 Cells to Cisplatin through AMPK-Dependent Inhibition of ERK and Akt Pathway","volume":"36","author":"Chen","year":"2015","journal-title":"Cell. Physiol. Biochem."},{"key":"ref_68","first-page":"2957","article-title":"Mannose shows antitumour properties against lung cancer via inhibiting proliferation, promoting cisplatin mediated apoptosis and reducing metastasis","volume":"22","author":"Wang","year":"2020","journal-title":"Mol. Med. Rep."},{"key":"ref_69","doi-asserted-by":"crossref","first-page":"8821","DOI":"10.2147\/OTT.S221161","article-title":"Motility and Apoptosis of Non-Small Cell Lung Cancer Cells Through ERK Signaling Pathway in Vitro and in Vivo","volume":"12","author":"Wang","year":"2019","journal-title":"OncoTargets Ther."},{"key":"ref_70","doi-asserted-by":"crossref","first-page":"456","DOI":"10.1002\/tox.22250","article-title":"Cinnamomum cassia Essential Oil and Its Major Constituent Cinnamaldehyde Induced Cell Cycle Arrest and Apoptosis in Human Oral Squamous Cell Carcinoma HSC-3 Cells","volume":"32","author":"Chang","year":"2016","journal-title":"Environ. Toxicol."},{"key":"ref_71","doi-asserted-by":"crossref","first-page":"726","DOI":"10.1002\/ptr.1190","article-title":"Antioxidant Activity of Cinnamomum cassia","volume":"17","author":"Lin","year":"2003","journal-title":"Phytother. Res."},{"key":"ref_72","doi-asserted-by":"crossref","first-page":"151","DOI":"10.4014\/jmb.1508.08024","article-title":"In Vitro Antiviral Activity of Cinnamomum cassia and Its Nanoparticles Against H7N3 Influenza A Virus","volume":"26","author":"Fatima","year":"2016","journal-title":"J. Microbiol. Biotechnol."},{"key":"ref_73","doi-asserted-by":"crossref","first-page":"115","DOI":"10.7150\/ijms.22293","article-title":"Cinnamomum cassia Extracts Suppress Human Lung Cancer Cells Invasion by Reducing u-PA\/MMP Expression through the FAK to ERK Pathways","volume":"15","author":"Wu","year":"2018","journal-title":"Int. J. Med. Sci."},{"key":"ref_74","doi-asserted-by":"crossref","first-page":"1905","DOI":"10.1016\/j.bmcl.2016.03.021","article-title":"Induction of apoptosis and differentiation by atractylenolide-1 isolated from Atractylodes macrocephala in human leukemia cells","volume":"26","author":"Huang","year":"2016","journal-title":"Bioorg. Med. Chem. Lett."},{"key":"ref_75","doi-asserted-by":"crossref","first-page":"420","DOI":"10.3109\/08923973.2014.968256","article-title":"Atractylenolide I inhibits lipopolysaccharide-induced inflammatory responses via mitogen-activated protein kinase pathways in RAW264.7 cells","volume":"36","author":"Ji","year":"2014","journal-title":"Immunopharmacol. Immunotoxicol."},{"key":"ref_76","doi-asserted-by":"crossref","first-page":"26","DOI":"10.1016\/j.yexcr.2017.02.040","article-title":"Atractylenolide I restores HO-1 expression and inhibits Ox-LDL-induced VSMCs proliferation, migration and inflammatory responses in vitro","volume":"353","author":"Li","year":"2017","journal-title":"Exp. Cell Res."},{"key":"ref_77","doi-asserted-by":"crossref","first-page":"13357","DOI":"10.3390\/molecules181113357","article-title":"Anti-Tumor Effects of Atractylenolide I Isolated from Atractylodes macrocephala in Human Lung Carcinoma Cell Lines","volume":"18","author":"Liu","year":"2013","journal-title":"Molecules"},{"key":"ref_78","doi-asserted-by":"crossref","first-page":"2353","DOI":"10.1159\/000484387","article-title":"Activation of ERK and Mutual Regulation of Stat3 and SP1 Contribute to Inhibition of PDK1 Expression by Atractylenolide-1 in Human Lung Cancer Cells","volume":"43","author":"Xiao","year":"2017","journal-title":"Cell. Physiol. Biochem."},{"key":"ref_79","doi-asserted-by":"crossref","first-page":"40","DOI":"10.1186\/s13046-016-0312-4","article-title":"Anti-tumor effects of Atractylenolide I on bladder cancer cells","volume":"35","author":"Yu","year":"2016","journal-title":"J. Exp. Clin. Cancer Res."},{"key":"ref_80","doi-asserted-by":"crossref","first-page":"222","DOI":"10.1111\/jcmm.12958","article-title":"Targeting EP4 downstream c-Jun through ERK1\/2-mediated reduction of DNMT1 reveals novel mechanism of solamargine inhibited growth of lung cancer cells","volume":"21","author":"Chen","year":"2016","journal-title":"J. Cell. Mol. Med."},{"key":"ref_81","first-page":"153","article-title":"Antihepatitis B Virus Constituents of Solanum erianthum","volume":"7","author":"Chou","year":"2012","journal-title":"Nat. Prod. Commun."},{"key":"ref_82","doi-asserted-by":"crossref","first-page":"161","DOI":"10.4103\/0973-1296.157721","article-title":"Effects of the extract and glycoalkaloids of Solanum lycocarpum St. Hill on Giardia lamblia trophozoites","volume":"11","author":"Martins","year":"2015","journal-title":"Pharmacogn. Mag."},{"key":"ref_83","doi-asserted-by":"crossref","first-page":"236","DOI":"10.1007\/s11418-013-0757-0","article-title":"Antiproliferative activity of Solanum lycocarpum alkaloidic extract and their constituents, solamargine and solasonine, in tumor cell lines","volume":"68","author":"Munari","year":"2013","journal-title":"J. Nat. Med."},{"key":"ref_84","doi-asserted-by":"crossref","first-page":"893","DOI":"10.1016\/j.tiv.2015.03.012","article-title":"Solamargine inhibits migration and invasion of human hepatocellular carcinoma cells through down-regulation of matrix metalloproteinases 2 and 9 expression and activity","volume":"29","author":"Sani","year":"2015","journal-title":"Toxicol. Vitr."},{"key":"ref_85","doi-asserted-by":"crossref","first-page":"8169","DOI":"10.1007\/s13277-014-2047-1","article-title":"Targeting signal transducer and activator of transcription 3 contributes to the solamargine-inhibited growth and-induced apoptosis of human lung cancer cells","volume":"35","author":"Zhou","year":"2014","journal-title":"Tumor Biol."},{"key":"ref_86","doi-asserted-by":"crossref","first-page":"56","DOI":"10.1078\/0944-7113-00376","article-title":"Anticonvulsant effects of thymoquinone, the major constituent of Nigella sativa seeds, in mice","volume":"11","author":"Hosseinzadeh","year":"2004","journal-title":"Phytomedicine"},{"key":"ref_87","doi-asserted-by":"crossref","first-page":"259","DOI":"10.1007\/s13277-014-2628-z","article-title":"Thymoquinone inhibits proliferation and invasion of human nonsmall-cell lung cancer cells via ERK pathway","volume":"36","author":"Yang","year":"2014","journal-title":"Tumor Biol."},{"key":"ref_88","doi-asserted-by":"crossref","first-page":"80","DOI":"10.1055\/s-2006-960446","article-title":"Synergistic Effects of the Alkaloid Sinomenine in Combination with the Immunosuppressive Drugs Tacrolimus and Mycophenolic Acid","volume":"65","author":"Vieregge","year":"1999","journal-title":"Planta Medica"},{"key":"ref_89","doi-asserted-by":"crossref","first-page":"1423","DOI":"10.1055\/s-2008-1081346","article-title":"Sinomenine Versus NSAIDs for the Treatment of Rheumatoid Arthritis: A Systematic Review and Meta-Analysis","volume":"74","author":"Xu","year":"2008","journal-title":"Planta Medica"},{"key":"ref_90","first-page":"1256","article-title":"Activation of PI3K\/Akt and ERK signaling pathways antagonized sinomenine-induced lung cancer cell apoptosis","volume":"5","author":"Zhou","year":"2012","journal-title":"Mol. Med. Rep."},{"key":"ref_91","first-page":"1525","article-title":"Anti-proliferative and antioxidant properties of rosemary Rosmarinus officinalis","volume":"17","author":"Cheung","year":"2007","journal-title":"Oncol. Rep."},{"key":"ref_92","doi-asserted-by":"crossref","unstructured":"O\u2019Neill, E.J., Moore, J., Song, J., and Tsiani, E.L. (2021). Inhibition of Non-Small Cell Lung Cancer Proliferation and Survival by Rosemary Extract Is Associated with Activation of ERKandAMPK. Life, 12.","DOI":"10.3390\/life12010052"},{"key":"ref_93","doi-asserted-by":"crossref","first-page":"243","DOI":"10.1007\/s11010-015-2331-4","article-title":"Maclurin suppresses migration and invasion of human non-small cell lung cancer cells via anti-oxidative activity and inhibition of the Src\/FAK\u2013ERK\u2013b-catenin pathway","volume":"402","author":"Ku","year":"2015","journal-title":"Mol. Cell. Biochem."},{"key":"ref_94","doi-asserted-by":"crossref","first-page":"149","DOI":"10.1186\/s12935-018-0646-4","article-title":"Marsdenia tenacissima extract induces apoptosis and suppresses autophagy through ERK activation in lung cancer cells","volume":"18","author":"Jiao","year":"2018","journal-title":"Cancer Cell Int."},{"key":"ref_95","doi-asserted-by":"crossref","first-page":"101978","DOI":"10.1016\/j.tranon.2024.101978","article-title":"TCF19 promotes cell proliferation and tumor formation in lung cancer by activating the Raf\/MEK\/ERK signaling pathway","volume":"45","author":"Tian","year":"2024","journal-title":"Transl. Oncol."},{"key":"ref_96","doi-asserted-by":"crossref","first-page":"e2400103","DOI":"10.1200\/PO.24.00103","article-title":"Phase II study of Ulixertinib in children and young adults with tumors harboring activating mitogen-activated protein kinase pathway alterations: APEC1621J of the national cancer institute-children\u2019s oncology group pediatric MATCH trial","volume":"8","author":"Vo","year":"2024","journal-title":"JCO Precis. Oncol."},{"key":"ref_97","doi-asserted-by":"crossref","first-page":"853","DOI":"10.1038\/nchembio.1629","article-title":"A unique inhibitor binding site in ERK1\/2 is associated with slow binding kinetics","volume":"10","author":"Chaikuad","year":"2014","journal-title":"Nat. Chem. Biol."},{"key":"ref_98","doi-asserted-by":"crossref","first-page":"12319","DOI":"10.1021\/acs.jmedchem.2c01044","article-title":"X-ray screening of an electrophilic fragment library and application toward the development of a novel ERK 1\/2 covalent inhibitor","volume":"65","author":"Denis","year":"2022","journal-title":"J. Med. Chem."},{"key":"ref_99","doi-asserted-by":"crossref","first-page":"e42287","DOI":"10.1097\/MD.0000000000042287","article-title":"Exploring the mechanisms of artemisinin and its derivatives in the treatment of atopic dermatitis based on network pharmacology and molecular docking","volume":"104","author":"Xu","year":"2025","journal-title":"Medicine"},{"key":"ref_100","first-page":"189","article-title":"Bioassay Screening and Binding Mode Study of Inhibitors Targeting at ERK2","volume":"40","author":"Wu","year":"2024","journal-title":"J. Guangxi Acad. Sci."},{"key":"ref_101","doi-asserted-by":"crossref","first-page":"15540","DOI":"10.1021\/acs.jmedchem.2c01361","article-title":"Targeting gatekeeper mutations for kinase drug discovery","volume":"65","author":"Zhou","year":"2022","journal-title":"J. Med. Chem."},{"key":"ref_102","doi-asserted-by":"crossref","first-page":"1615","DOI":"10.1021\/acs.jctc.2c01171","article-title":"Strategy toward kinase-selective drug discovery","volume":"19","author":"Zhang","year":"2023","journal-title":"J. Chem. Theory Comput."}],"container-title":["Pharmaceuticals"],"original-title":[],"language":"en","link":[{"URL":"https:\/\/www.mdpi.com\/1424-8247\/18\/9\/1371\/pdf","content-type":"unspecified","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2025,10,9]],"date-time":"2025-10-09T18:44:58Z","timestamp":1760035498000},"score":1,"resource":{"primary":{"URL":"https:\/\/www.mdpi.com\/1424-8247\/18\/9\/1371"}},"subtitle":[],"short-title":[],"issued":{"date-parts":[[2025,9,12]]},"references-count":102,"journal-issue":{"issue":"9","published-online":{"date-parts":[[2025,9]]}},"alternative-id":["ph18091371"],"URL":"https:\/\/doi.org\/10.3390\/ph18091371","relation":{},"ISSN":["1424-8247"],"issn-type":[{"value":"1424-8247","type":"electronic"}],"subject":[],"published":{"date-parts":[[2025,9,12]]}}}