{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,10,11]],"date-time":"2026-10-11T03:38:55Z","timestamp":1791689935135,"version":"4.3.4"},"reference-count":44,"publisher":"MDPI AG","issue":"6","license":[{"start":{"date-parts":[[2023,5,31]],"date-time":"2023-05-31T00:00:00Z","timestamp":1685491200000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"funder":[{"name":"National Research Foundation of Korea (NRF), with a grant provided by the Korean government (MSIT)","award":["NRF-2021R1C1C1011799"],"award-info":[{"award-number":["NRF-2021R1C1C1011799"]}]},{"name":"National Research Foundation of Korea (NRF), with a grant provided by the Korean government (MSIT)","award":["NRF-2021R1I1A3A04037158"],"award-info":[{"award-number":["NRF-2021R1I1A3A04037158"]}]}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":["Life"],"abstract":"<jats:p>The natural product Kochiae Fructus (KF) is the ripe fruit of Kochia scoparia (L.) Schrad and is renowned for its anti-inflammatory, anticancer, anti-fungal, and anti-pruritic effects. This study examined the anticancer effect of components of KF to assess its potential as an adjuvant for cancer treatment. Network-based pharmacological and docking analyses of KF found associations with oral squamous cell carcinoma. The molecular docking of oleanolic acid (OA) with LC3 and SQSTM1 had high binding scores, and hydrogen binding with amino acids of the receptors suggests that OA is involved in autophagy, rather than the apoptosis pathway. For experimental validation, we exposed SCC-15 squamous carcinoma cells derived from a human tongue lesion to KF extract (KFE), OA, and cisplatin. The KFE caused SCC-15 cell death, and induced an accumulation of the autophagy marker proteins LC3 and p62\/SQSTM1. The novelty of this study lies in the discovery that the change in autophagy protein levels can be related to the regulatory death of SCC-15 cells. These findings suggest that KF is a promising candidate for future studies to provide insight into the role of autophagy in cancer cells and advance our understanding of cancer prevention and treatment.<\/jats:p>","DOI":"10.3390\/life13061300","type":"journal-article","created":{"date-parts":[[2023,6,1]],"date-time":"2023-06-01T01:40:56Z","timestamp":1685583656000},"page":"1300","update-policy":"https:\/\/doi.org\/10.3390\/mdpi_crossmark_policy","source":"Crossref","is-referenced-by-count":3,"title":["Discovering Potential Anti-Oral Squamous Cell Carcinoma Mechanisms from Kochiae Fructus Using Network-Based Pharmacology Analysis and Experimental Validation"],"prefix":"10.3390","volume":"13","author":[{"given":"Youn-Sook","family":"Kim","sequence":"first","affiliation":[{"name":"Research Institute for Longevity and Well-Being, Pusan National University, Busan 46241, Republic of Korea"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Jin-Choon","family":"Lee","sequence":"additional","affiliation":[{"name":"Department of Otolaryngology-Head and Neck Surgery, College of Medicine, Pusan National University and Research Institute for Convergence of Biomedical Science and Technology, Pusan National University Yangsan Hospital, Yangsan 50612, Republic of Korea"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Minhyung","family":"Lee","sequence":"additional","affiliation":[{"name":"Department of Otolaryngology-Head and Neck Surgery, College of Medicine, Pusan National University and Research Institute for Convergence of Biomedical Science and Technology, Pusan National University Yangsan Hospital, Yangsan 50612, Republic of Korea"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Hae-Jin","family":"Oh","sequence":"additional","affiliation":[{"name":"Department of Otolaryngology-Head and Neck Surgery, College of Medicine, Pusan National University and Research Institute for Convergence of Biomedical Science and Technology, Pusan National University Yangsan Hospital, Yangsan 50612, Republic of Korea"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-1341-2114","authenticated-orcid":false,"given":"Won G.","family":"An","sequence":"additional","affiliation":[{"name":"Department of Pharmacology, School of Korean Medicine, Pusan National University, Yangsan 50612, Republic of Korea"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-8752-3426","authenticated-orcid":false,"given":"Eui-Suk","family":"Sung","sequence":"additional","affiliation":[{"name":"Department of Otolaryngology-Head and Neck Surgery, College of Medicine, Pusan National University and Research Institute for Convergence of Biomedical Science and Technology, Pusan National University Yangsan Hospital, Yangsan 50612, Republic of Korea"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"1968","published-online":{"date-parts":[[2023,5,31]]},"reference":[{"key":"ref_1","doi-asserted-by":"crossref","first-page":"209","DOI":"10.3322\/caac.21660","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. Clin."},{"key":"ref_2","first-page":"275","article-title":"Activation of programmed cell death by anticancer agents: Cisplatin as a model system","volume":"2","author":"Eastman","year":"1990","journal-title":"Cancer Cells"},{"key":"ref_3","doi-asserted-by":"crossref","first-page":"103","DOI":"10.1159\/000085769","article-title":"Effects of cisplatin, 5-fluorouracil, and radiation on cell cycle regulation and apoptosis in the hypopharyngeal carcinoma cell line","volume":"51","author":"Lee","year":"2005","journal-title":"Chemotherapy"},{"key":"ref_4","doi-asserted-by":"crossref","first-page":"1980","DOI":"10.1200\/JCO.21.01293","article-title":"Weekly Cisplatin Plus Radiation for Postoperative Head and Neck Cancer (JCOG1008): A Multicenter, Noninferiority, Phase II\/III Randomized Controlled Trial","volume":"40","author":"Kiyota","year":"2022","journal-title":"J. Clin. Oncol."},{"key":"ref_5","doi-asserted-by":"crossref","first-page":"49","DOI":"10.2174\/187152012798764697","article-title":"Natural products: Promising resources for cancer drug discovery","volume":"12","author":"Mondal","year":"2012","journal-title":"Anticancer Agents Med. Chem."},{"key":"ref_6","doi-asserted-by":"crossref","first-page":"17","DOI":"10.1007\/s40484-019-0167-8","article-title":"A survey of web resources and tools for the study of TCM network pharmacology","volume":"7","author":"Zhao","year":"2019","journal-title":"Quant. Biol."},{"key":"ref_7","doi-asserted-by":"crossref","first-page":"687","DOI":"10.1111\/j.1751-7915.2010.00221.x","article-title":"Natural products for cancer chemotherapy","volume":"4","author":"Demain","year":"2011","journal-title":"Microb. Biotechnol."},{"key":"ref_8","doi-asserted-by":"crossref","unstructured":"Li, Y., Li, S., Meng, X., Gan, R.Y., Zhang, J.J., and Li, H.B. (2017). Dietary Natural Products for Prevention and Treatment of Breast Cancer. Nutrients, 9.","DOI":"10.3390\/nu9070728"},{"key":"ref_9","doi-asserted-by":"crossref","first-page":"1165","DOI":"10.1248\/bpb.20.1165","article-title":"Studies on kochiae fructus. IV. Anti-allergic effects of 70% ethanol extract and its component, momordin Ic from dried fruits of Kochia scoparia L","volume":"20","author":"Matsuda","year":"1997","journal-title":"Biol. Pharm. Bull."},{"key":"ref_10","doi-asserted-by":"crossref","first-page":"5382684","DOI":"10.1155\/2021\/5382684","article-title":"Kochiae Fructus, the Fruit of Common Potherb Kochia scoparia (L.) Schrad: A Review on Phytochemistry, Pharmacology, Toxicology, Quality Control, and Pharmacokinetics","volume":"2021","author":"Zou","year":"2021","journal-title":"Evid.-Based Complement. Alternat. Med."},{"key":"ref_11","doi-asserted-by":"crossref","first-page":"1096920","DOI":"10.1155\/2018\/1096920","article-title":"The Anti-Inflammatory Effect of Fructus Kochiae on Allergic Contact Dermatitis Rats via pERK1\/2\/TLR4\/NF-kappaB Pathway Activation","volume":"2018","author":"Xiao","year":"2018","journal-title":"Evid.-Based Complement. Alternat. Med."},{"key":"ref_12","doi-asserted-by":"crossref","first-page":"684","DOI":"10.1080\/13880209.2019.1672753","article-title":"Kochia scoparia seed extract suppresses VEGF-induced angiogenesis via modulating VEGF receptor 2 and PI3K\/AKT\/mTOR pathways","volume":"57","author":"Cho","year":"2019","journal-title":"Pharm. Biol."},{"key":"ref_13","doi-asserted-by":"crossref","unstructured":"Houlihan, A.J., Conlin, P., and Chee-Sanford, J.C. (2019). Water-soluble exudates from seeds of Kochia scoparia exhibit antifungal activity against Colletotrichum graminicola. PLoS ONE, 14.","DOI":"10.1371\/journal.pone.0218104"},{"key":"ref_14","doi-asserted-by":"crossref","first-page":"193","DOI":"10.1248\/yakushi1947.117.4_193","article-title":"Studies on Kochiae Fructus. I. Antipruritogenic effect of 70% ethanol extract from kochiae fructus and its active component","volume":"117","author":"Kubo","year":"1997","journal-title":"Yakugaku Zasshi"},{"key":"ref_15","doi-asserted-by":"crossref","first-page":"751","DOI":"10.1007\/s10495-013-0820-z","article-title":"Momordin Ic induces HepG2 cell apoptosis through MAPK and PI3K\/Akt-mediated mitochondrial pathways","volume":"18","author":"Wang","year":"2013","journal-title":"Apoptosis"},{"key":"ref_16","doi-asserted-by":"crossref","first-page":"118395","DOI":"10.1016\/j.lfs.2020.118395","article-title":"Hispidulin: A promising flavonoid with diverse anti-cancer properties","volume":"259","author":"Liu","year":"2020","journal-title":"Life Sci."},{"key":"ref_17","doi-asserted-by":"crossref","first-page":"123","DOI":"10.3389\/fphar.2019.00123","article-title":"Network Pharmacology Databases for Traditional Chinese Medicine: Review and Assessment","volume":"10","author":"Zhang","year":"2019","journal-title":"Front. Pharmacol."},{"key":"ref_18","doi-asserted-by":"crossref","first-page":"1523","DOI":"10.1038\/s41467-019-09234-6","article-title":"Metascape provides a biologist-oriented resource for the analysis of systems-level datasets","volume":"10","author":"Zhou","year":"2019","journal-title":"Nat. Commun."},{"key":"ref_19","doi-asserted-by":"crossref","first-page":"D1110","DOI":"10.1093\/nar\/gky1021","article-title":"SymMap: An integrative database of traditional Chinese medicine enhanced by symptom mapping","volume":"47","author":"Wu","year":"2019","journal-title":"Nucleic Acids Res."},{"key":"ref_20","doi-asserted-by":"crossref","first-page":"13","DOI":"10.1186\/1758-2946-6-13","article-title":"TCMSP: A database of systems pharmacology for drug discovery from herbal medicines","volume":"6","author":"Ru","year":"2014","journal-title":"J. Cheminform."},{"key":"ref_21","doi-asserted-by":"crossref","first-page":"D1238","DOI":"10.1093\/nar\/gkab1011","article-title":"HIT 2.0: An enhanced platform for Herbal Ingredients\u2019Targets","volume":"50","author":"Yan","year":"2022","journal-title":"Nucleic Acids Res."},{"key":"ref_22","doi-asserted-by":"crossref","first-page":"D1197","DOI":"10.1093\/nar\/gkaa1063","article-title":"HERB: A high-throughput experiment- and reference-guided database of traditional Chinese medicine","volume":"49","author":"Fang","year":"2021","journal-title":"Nucleic Acids Res."},{"key":"ref_23","doi-asserted-by":"crossref","first-page":"6964","DOI":"10.3390\/ijms13066964","article-title":"A novel chemometric method for the prediction of human oral bioavailability","volume":"13","author":"Xu","year":"2012","journal-title":"Int. J. Mol. Sci."},{"key":"ref_24","doi-asserted-by":"crossref","first-page":"31","DOI":"10.1186\/1758-2946-4-31","article-title":"Drug-likeness analysis of traditional Chinese medicines: 1. property distributions of drug-like compounds, non-drug-like compounds and natural compounds from traditional Chinese medicines","volume":"4","author":"Shen","year":"2012","journal-title":"J. Cheminform."},{"key":"ref_25","doi-asserted-by":"crossref","first-page":"2111","DOI":"10.1038\/nprot.2007.303","article-title":"Determination of drug permeability and prediction of drug absorption in Caco-2 monolayers","volume":"2","author":"Hubatsch","year":"2007","journal-title":"Nat. Protoc."},{"key":"ref_26","doi-asserted-by":"crossref","unstructured":"Attique, S.A., Hassan, M., Usman, M., Atif, R.M., Mahboob, S., Al-Ghanim, K.A., Bilal, M., and Nawaz, M.Z. (2019). A Molecular Docking Approach to Evaluate the Pharmacological Properties of Natural and Synthetic Treatment Candidates for Use against Hypertension. Int. J. Environ. Res. Public. Health, 16.","DOI":"10.3390\/ijerph16060923"},{"key":"ref_27","doi-asserted-by":"crossref","first-page":"42717","DOI":"10.1038\/srep42717","article-title":"SwissADME: A free web tool to evaluate pharmacokinetics, drug-likeness and medicinal chemistry friendliness of small molecules","volume":"7","author":"Daina","year":"2017","journal-title":"Sci. Rep."},{"key":"ref_28","doi-asserted-by":"crossref","first-page":"20","DOI":"10.1186\/s13321-016-0130-x","article-title":"Improving chemical similarity ensemble approach in target prediction","volume":"8","author":"Wang","year":"2016","journal-title":"J. Cheminform."},{"key":"ref_29","doi-asserted-by":"crossref","unstructured":"UniProt Consortium (2019). UniProt: A worldwide hub of protein knowledge. Nucleic Acids Res., 47, D506\u2013D515.","DOI":"10.1093\/nar\/gky1049"},{"key":"ref_30","doi-asserted-by":"crossref","first-page":"3891","DOI":"10.1021\/acs.jcim.1c00203","article-title":"AutoDock Vina 1.2.0: New Docking Methods, Expanded Force Field, and Python Bindings","volume":"61","author":"Eberhardt","year":"2021","journal-title":"J. Chem. Inf. Model."},{"key":"ref_31","doi-asserted-by":"crossref","first-page":"455","DOI":"10.1002\/jcc.21334","article-title":"AutoDock Vina: Improving the speed and accuracy of docking with a new scoring function, efficient optimization, and multithreading","volume":"31","author":"Trott","year":"2010","journal-title":"J. Comput. Chem."},{"key":"ref_32","doi-asserted-by":"crossref","first-page":"2778","DOI":"10.1021\/ci200227u","article-title":"LigPlot+: Multiple ligand-protein interaction diagrams for drug discovery","volume":"51","author":"Laskowski","year":"2011","journal-title":"J. Chem. Inf. Model."},{"key":"ref_33","doi-asserted-by":"crossref","first-page":"531","DOI":"10.1042\/bj20031229","article-title":"Binding of phosphatidylinositol 3,4,5-trisphosphate to the pleckstrin homology domain of protein kinase B induces a conformational change","volume":"375","author":"Milburn","year":"2003","journal-title":"Biochem. J."},{"key":"ref_34","doi-asserted-by":"crossref","first-page":"5447","DOI":"10.1074\/jbc.RA117.000728","article-title":"Modifications to a common phosphorylation network provide individualized control in caspases","volume":"293","author":"Thomas","year":"2018","journal-title":"J. Biol. Chem."},{"key":"ref_35","doi-asserted-by":"crossref","first-page":"611","DOI":"10.1111\/j.1356-9597.2004.00750.x","article-title":"The crystal structure of microtubule-associated protein light chain 3, a mammalian homologue of Saccharomyces cerevisiae Atg8","volume":"9","author":"Sugawara","year":"2004","journal-title":"Genes Cells"},{"key":"ref_36","first-page":"729","article-title":"Oligomer Model of PB1 Domain of p62\/SQSTM1 Based on Crystal Structure of Homo-Dimer and Calculation of Helical Characteristics","volume":"42","author":"Lim","year":"2019","journal-title":"Mol. Cells"},{"key":"ref_37","doi-asserted-by":"crossref","unstructured":"Pan, H.L.M., Yang, Y., Callaway, K., Baker, J., Diep, L., Yan, J., Tanaka, K., Zhu, Y.L., Konradi, A.W., and Jobling, M. (2013). Crystal Structures of apo Keap1, Keap1-peptide, and Keap1-compound complexes. Acta Crystallogr. D Biol. Crystallogr.","DOI":"10.2210\/pdb4ifl\/pdb"},{"key":"ref_38","doi-asserted-by":"crossref","first-page":"323","DOI":"10.1016\/S0092-8674(00)81663-3","article-title":"Crystal structure of the PTEN tumor suppressor: Implications for its phosphoinositide phosphatase activity and membrane association","volume":"99","author":"Lee","year":"1999","journal-title":"Cell"},{"key":"ref_39","doi-asserted-by":"crossref","first-page":"92","DOI":"10.1038\/s41572-020-00224-3","article-title":"Head and neck squamous cell carcinoma","volume":"6","author":"Johnson","year":"2020","journal-title":"Nat. Rev. Dis. Primers"},{"key":"ref_40","doi-asserted-by":"crossref","first-page":"127","DOI":"10.1016\/j.canlet.2020.10.007","article-title":"Palmitic acid negatively regulates tumor suppressor PTEN through T366 phosphorylation and protein degradation","volume":"496","author":"Bai","year":"2021","journal-title":"Cancer Lett."},{"key":"ref_41","doi-asserted-by":"crossref","first-page":"369","DOI":"10.1016\/j.etp.2005.02.003","article-title":"Saturated free fatty acid, palmitic acid, induces apoptosis in fetal hepatocytes in culture","volume":"56","author":"Ji","year":"2005","journal-title":"Exp. Toxicol. Pathol."},{"key":"ref_42","doi-asserted-by":"crossref","first-page":"259","DOI":"10.1211\/0022357055407","article-title":"Oleanolic acid nanosuspensions: Preparation, in-vitro characterization and enhanced hepatoprotective effect","volume":"57","author":"Chen","year":"2005","journal-title":"J. Pharm. Pharmacol."},{"key":"ref_43","doi-asserted-by":"crossref","first-page":"10","DOI":"10.1016\/j.phytochem.2011.12.022","article-title":"Oleanolic acid","volume":"77","author":"Pollier","year":"2012","journal-title":"Phytochemistry"},{"key":"ref_44","doi-asserted-by":"crossref","first-page":"26370","DOI":"10.18632\/oncotarget.25316","article-title":"Oleanolic acid induces p53-dependent apoptosis via the ERK\/JNK\/AKT pathway in cancer cell lines in prostatic cancer xenografts in mice","volume":"9","author":"Kim","year":"2018","journal-title":"Oncotarget"}],"container-title":["Life"],"original-title":[],"language":"en","link":[{"URL":"https:\/\/www.mdpi.com\/2075-1729\/13\/6\/1300\/pdf","content-type":"unspecified","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2025,10,10]],"date-time":"2025-10-10T19:46:30Z","timestamp":1760125590000},"score":1,"resource":{"primary":{"URL":"https:\/\/www.mdpi.com\/2075-1729\/13\/6\/1300"}},"subtitle":[],"short-title":[],"issued":{"date-parts":[[2023,5,31]]},"references-count":44,"journal-issue":{"issue":"6","published-online":{"date-parts":[[2023,6]]}},"alternative-id":["life13061300"],"URL":"https:\/\/doi.org\/10.3390\/life13061300","relation":{},"ISSN":["2075-1729"],"issn-type":[{"value":"2075-1729","type":"electronic"}],"subject":[],"published":{"date-parts":[[2023,5,31]]}}}