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EF-hand domain-containing protein D2 (EFHD2) has been recently shown to increase cisplatin resistance and is significantly associated with recurrence in early-stage NSCLC patients. Natural products, commonly used as phytonutrients, are also recognized for their potential as pharmaceutical anticancer agents. Result: In this study, a range of Chinese herbs known for their antitumor or chemotherapy-enhancing properties were evaluated for their ability to inhibit EFHD2 expression in NSCLC cells. Among the herbs tested, Stephania tetrandra (S. tetrandra) exhibited the highest efficacy in inhibiting EFHD2 and sensitizing cells to cisplatin. Through LC-MS identification and functional assays, coclaurine was identified as a key molecule in S. tetrandra responsible for EFHD2 inhibition. Coclaurine not only downregulated EFHD2-related NOX4-ABCC1 signaling and enhanced cisplatin sensitivity, but also suppressed the stemness and metastatic properties of NSCLC cells. Mechanistically, coclaurine disrupted the interaction between the transcription factor FOXG1 and the EFHD2 promoter, leading to a reduction in EFHD2 transcription. Silencing FOXG1 further inhibited EFHD2 expression and sensitized NSCLC cells to cisplatin. Conclusions:\u00a0S. tetrandra and its active compound coclaurine may serve as effective adjuvant therapies to improve cisplatin efficacy in the treatment of NSCLC.<\/jats:p>","DOI":"10.3390\/ph17101356","type":"journal-article","created":{"date-parts":[[2024,10,11]],"date-time":"2024-10-11T03:53:47Z","timestamp":1728618827000},"page":"1356","update-policy":"https:\/\/doi.org\/10.3390\/mdpi_crossmark_policy","source":"Crossref","is-referenced-by-count":4,"title":["Stephania tetrandra and Its Active Compound Coclaurine Sensitize NSCLC Cells to Cisplatin through EFHD2 Inhibition"],"prefix":"10.3390","volume":"17","author":[{"ORCID":"https:\/\/orcid.org\/0009-0002-5220-2846","authenticated-orcid":false,"given":"Shu-Yu","family":"Hu","sequence":"first","affiliation":[{"name":"Graduate Institute of Biomedical Sciences, China Medical University, Taichung 404333, Taiwan"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Tsai-Hui","family":"Lin","sequence":"additional","affiliation":[{"name":"Department of Chinese Medicine, China Medical University Hospital, Taichung 404327, Taiwan"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-1725-0079","authenticated-orcid":false,"given":"Chung-Yu","family":"Chen","sequence":"additional","affiliation":[{"name":"Research Center for Cancer Biology, China Medical University, Taichung 406040, Taiwan"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-6355-3006","authenticated-orcid":false,"given":"Yu-Hao","family":"He","sequence":"additional","affiliation":[{"name":"Graduate Institute of Biomedical Sciences, China Medical University, Taichung 404333, Taiwan"},{"name":"Center for Molecular Medicine, China Medical University Hospital, Taichung 406040, Taiwan"},{"name":"Program for Cancer Biology and Drug Discovery, China Medical University, Taichung 404333, Taiwan"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-6467-8716","authenticated-orcid":false,"given":"Wei-Chien","family":"Huang","sequence":"additional","affiliation":[{"name":"Graduate Institute of Biomedical Sciences, China Medical University, Taichung 404333, Taiwan"},{"name":"Center for Molecular Medicine, China Medical University Hospital, Taichung 406040, Taiwan"},{"name":"Program for Cancer Biology and Drug Discovery, China Medical University, Taichung 404333, Taiwan"},{"name":"School of Pharmacy, China Medical University, Taichung 404333, Taiwan"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Ching-Yun","family":"Hsieh","sequence":"additional","affiliation":[{"name":"Division of Hematology and Oncology, Department of internal medicine, China Medical University Hospital, Taichung 404327, Taiwan"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Ya-Huey","family":"Chen","sequence":"additional","affiliation":[{"name":"Graduate Institute of Biomedical Sciences, China Medical University, Taichung 404333, Taiwan"},{"name":"Center for Molecular Medicine, China Medical University Hospital, Taichung 406040, Taiwan"},{"name":"Program for Cancer Biology and Drug Discovery, China Medical University, Taichung 404333, Taiwan"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-1669-0037","authenticated-orcid":false,"given":"Wei-Chao","family":"Chang","sequence":"additional","affiliation":[{"name":"Center for Molecular Medicine, China Medical University Hospital, Taichung 406040, Taiwan"}],"role":[{"role":"author","vocabulary":"crossref"}]}],"member":"1968","published-online":{"date-parts":[[2024,10,11]]},"reference":[{"key":"ref_1","doi-asserted-by":"crossref","first-page":"7","DOI":"10.3322\/caac.21654","article-title":"Cancer Statistics, 2021","volume":"71","author":"Siegel","year":"2021","journal-title":"CA Cancer J. Clin."},{"key":"ref_2","doi-asserted-by":"crossref","first-page":"953","DOI":"10.6004\/jnccn.2022.7021","article-title":"Perioperative Systemic Therapy for Resectable Non-Small Cell Lung Cancer","volume":"20","author":"Muthusamy","year":"2022","journal-title":"J. Natl. Compr. Canc. Netw."},{"key":"ref_3","doi-asserted-by":"crossref","first-page":"e278S","DOI":"10.1378\/chest.12-2359","article-title":"Treatment of stage I and II non-small cell lung cancer: Diagnosis and management of lung cancer, 3rd ed: American College of Chest Physicians evidence-based clinical practice guidelines","volume":"143","author":"Howington","year":"2013","journal-title":"Chest"},{"key":"ref_4","first-page":"242","article-title":"Recurrence after surgery in patients with NSCLC","volume":"3","author":"Uramoto","year":"2014","journal-title":"Transl. Lung Cancer Res."},{"key":"ref_5","doi-asserted-by":"crossref","first-page":"iv1","DOI":"10.1093\/annonc\/mdx222","article-title":"Early and locally advanced non-small-cell lung cancer (NSCLC): ESMO Clinical Practice Guidelines for diagnosis, treatment and follow-up","volume":"28","author":"Postmus","year":"2017","journal-title":"Ann. Oncol."},{"key":"ref_6","doi-asserted-by":"crossref","unstructured":"NSCLC Meta-analysis Collaborative Group (2014). Preoperative chemotherapy for non-small-cell lung cancer: A systematic review and meta-analysis of individual participant data. Lancet, 383, 1561\u20131571.","DOI":"10.1016\/S0140-6736(13)62159-5"},{"key":"ref_7","doi-asserted-by":"crossref","first-page":"4841","DOI":"10.1007\/s00018-013-1447-5","article-title":"Swiprosin-1 modulates actin dynamics by regulating the F-actin accessibility to cofilin","volume":"70","author":"Huh","year":"2013","journal-title":"Cell. Mol. Life Sci."},{"key":"ref_8","doi-asserted-by":"crossref","first-page":"1282","DOI":"10.1038\/s41467-024-45539-x","article-title":"EFHD2 suppresses intestinal inflammation by blocking intestinal epithelial cell TNFR1 internalization and cell death","volume":"15","author":"Wu","year":"2024","journal-title":"Nat. Commun."},{"key":"ref_9","doi-asserted-by":"crossref","first-page":"13060","DOI":"10.18632\/oncotarget.3637","article-title":"Swiprosin-1 stimulates cancer invasion and metastasis by increasing the Rho family of GTPase signaling","volume":"6","author":"Huh","year":"2015","journal-title":"Oncotarget"},{"key":"ref_10","doi-asserted-by":"crossref","unstructured":"Fan, C.C., Cheng, W.C., Huang, Y.C., Sher, Y.P., Liou, N.J., Chien, Y.C., Lin, P.S., Lin, P.S., Chen, C.H., and Chang, W.C. (2017). EFHD2 promotes epithelial-to-mesenchymal transition and correlates with postsurgical recurrence of stage I lung adenocarcinoma. Sci. Rep., 7.","DOI":"10.1038\/s41598-017-15186-y"},{"key":"ref_11","doi-asserted-by":"crossref","unstructured":"Fan, C.C., Tsai, S.T., Lin, C.Y., Chang, L.C., Yang, J.C., Chen, G.Y., Sher, Y.P., Wang, S.C., Hsiao, M., and Chang, W.C. (2020). EFHD2 contributes to non-small cell lung cancer cisplatin resistance by the activation of NOX4-ROS-ABCC1 axis. Redox Biol., 34.","DOI":"10.1016\/j.redox.2020.101571"},{"key":"ref_12","doi-asserted-by":"crossref","first-page":"779","DOI":"10.1016\/j.phymed.2012.03.005","article-title":"Curcumin reverses cisplatin resistance and promotes human lung adenocarcinoma A549\/DDP cell apoptosis through HIF-1\u03b1 and caspase-3 mechanisms","volume":"19","author":"Ye","year":"2012","journal-title":"Phytomedicine"},{"key":"ref_13","doi-asserted-by":"crossref","first-page":"e1027","DOI":"10.1038\/cddis.2013.550","article-title":"Ibuprofen enhances the anticancer activity of cisplatin in lung cancer cells by inhibiting the heat shock protein 70","volume":"5","author":"Endo","year":"2014","journal-title":"Cell Death Dis."},{"key":"ref_14","doi-asserted-by":"crossref","first-page":"e12442","DOI":"10.1097\/MD.0000000000012442","article-title":"Effects of postoperative non-steroidal anti-inflammatory drugs on long-term survival and recurrence of patients with non-small cell lung cancer","volume":"97","author":"Jiang","year":"2018","journal-title":"Medicine"},{"key":"ref_15","doi-asserted-by":"crossref","first-page":"252","DOI":"10.1093\/jnci\/94.4.252","article-title":"Nonsteroidal anti-inflammatory drugs as anticancer agents: Mechanistic, pharmacologic, and clinical issues","volume":"94","author":"Thun","year":"2002","journal-title":"J. Natl. Cancer Inst."},{"key":"ref_16","doi-asserted-by":"crossref","unstructured":"Ekor, M. (2014). The growing use of herbal medicines: Issues relating to adverse reactions and challenges in monitoring safety. Front. Pharmacol., 4.","DOI":"10.3389\/fphar.2013.00177"},{"key":"ref_17","doi-asserted-by":"crossref","first-page":"1","DOI":"10.1158\/1940-6207.CAPR-14-0160","article-title":"Toxic phytochemicals and their potential risks for human cancer","volume":"8","author":"Bode","year":"2015","journal-title":"Cancer Prev. Res."},{"key":"ref_18","doi-asserted-by":"crossref","unstructured":"Fridlender, M., Kapulnik, Y., and Koltai, H. (2015). Plant derived substances with anti-cancer activity: From folklore to practice. Front. Plant Sci., 6.","DOI":"10.3389\/fpls.2015.00799"},{"key":"ref_19","doi-asserted-by":"crossref","first-page":"1409","DOI":"10.1111\/bph.14816","article-title":"Natural compounds as potential adjuvants to cancer therapy: Preclinical evidence","volume":"177","author":"Lin","year":"2020","journal-title":"Br. J. Pharmacol."},{"key":"ref_20","doi-asserted-by":"crossref","first-page":"112995","DOI":"10.1016\/j.jep.2020.112995","article-title":"History of uses, phytochemistry, pharmacological activities, quality control and toxicity of the root of Stephania tetrandra S. Moore: A review","volume":"260","author":"Zhang","year":"2020","journal-title":"J. Ethnopharmacol."},{"key":"ref_21","doi-asserted-by":"crossref","first-page":"449","DOI":"10.1007\/s11101-020-09673-w","article-title":"A critical review: Traditional uses, phytochemistry, pharmacology and toxicology of Stephania tetrandra S. Moore (Fen Fang Ji)","volume":"19","author":"Jiang","year":"2020","journal-title":"Phytochem. Rev."},{"key":"ref_22","doi-asserted-by":"crossref","first-page":"88","DOI":"10.1016\/j.abb.2017.06.023","article-title":"The family of berberine bridge enzyme-like enzymes: A treasure-trove of oxidative reactions","volume":"632","author":"Daniel","year":"2017","journal-title":"Arch. Biochem. Biophys."},{"key":"ref_23","doi-asserted-by":"crossref","unstructured":"Kong, X.P., Ren, H.Q., Liu, E.Y.L., Leung, K.W., Guo, S.C., Duan, R., Dong, T.T.X., and Tsim, K.W.K. (2020). The Cholinesterase Inhibitory Properties of Stephaniae Tetrandrae Radix. Molecules, 25.","DOI":"10.3390\/molecules25245914"},{"key":"ref_24","doi-asserted-by":"crossref","first-page":"311","DOI":"10.1016\/j.joim.2021.01.001","article-title":"An overview on the chemistry, pharmacology and anticancer properties of tetrandrine and fangchinoline (alkaloids) from Stephania tetrandra roots","volume":"19","author":"Chan","year":"2021","journal-title":"J. Integr. Med."},{"key":"ref_25","doi-asserted-by":"crossref","first-page":"105743","DOI":"10.1016\/j.antiviral.2023.105743","article-title":"Fangchinoline inhibits SARS-CoV-2 and MERS-CoV entry","volume":"220","author":"Sadhu","year":"2023","journal-title":"Antivir. Res."},{"key":"ref_26","doi-asserted-by":"crossref","first-page":"100972","DOI":"10.1016\/j.jpha.2024.100972","article-title":"Fangchinoline induces antiviral response by suppressing STING degradation","volume":"14","author":"Wang","year":"2024","journal-title":"J. Pharm. Anal."},{"key":"ref_27","doi-asserted-by":"crossref","first-page":"164","DOI":"10.1016\/j.canlet.2018.03.042","article-title":"Tetrandrine inhibits deregulated cell cycle in pancreatic cancer cells: Differential regulation of p21Cip1\/Waf1, p27Kip1 and cyclin D1","volume":"425","author":"Singh","year":"2018","journal-title":"Cancer Lett."},{"key":"ref_28","doi-asserted-by":"crossref","first-page":"385","DOI":"10.1142\/S0192415X17500240","article-title":"Stephania Tetrandra and Ginseng-Containing Chinese Herbal Formulation NSENL Reverses Cisplatin Resistance in Lung Cancer Xenografts","volume":"45","author":"Jin","year":"2017","journal-title":"Am. J. Chin. Med."},{"key":"ref_29","doi-asserted-by":"crossref","first-page":"2146","DOI":"10.2174\/1871520623666230831103936","article-title":"QSAR Research of Novel Tetrandrine Derivatives against Human Hepatocellular Carcinoma","volume":"23","author":"Wang","year":"2023","journal-title":"Anticancer Agents Med. Chem."},{"key":"ref_30","doi-asserted-by":"crossref","first-page":"117","DOI":"10.1007\/s11418-007-0200-5","article-title":"Authentication of Stephania tetrandra S. Moore (Fang Ji) and differentiation of its common adulterants using microscopy and HPLC analysis","volume":"62","author":"Joshi","year":"2008","journal-title":"J. Nat. Med."},{"key":"ref_31","doi-asserted-by":"crossref","first-page":"148","DOI":"10.1016\/j.aca.2013.01.001","article-title":"Simultaneous determination of fangchinoline and tetrandrine in Stephania tetrandra S. Moore by using 1-alkyl-3-methylimidazolium-based ionic liquids as the RP-HPLC mobile phase additives","volume":"767","author":"Tang","year":"2013","journal-title":"Anal. Chim. Acta."},{"key":"ref_32","doi-asserted-by":"crossref","first-page":"247","DOI":"10.1016\/j.semcancer.2005.04.002","article-title":"Arginine deprivation and metabolomics: Important aspects of intermediary metabolism in relation to the differential sensitivity of normal and tumour cells","volume":"15","author":"Wheatley","year":"2005","journal-title":"Semin. Cancer Biol."},{"key":"ref_33","doi-asserted-by":"crossref","first-page":"2315","DOI":"10.1038\/nprot.2006.339","article-title":"Clonogenic assay of cells in vitro","volume":"1","author":"Franken","year":"2006","journal-title":"Nat. Protoc."},{"key":"ref_34","doi-asserted-by":"crossref","first-page":"119465","DOI":"10.1016\/j.lfs.2021.119465","article-title":"Cancer stem cells targets and combined therapies to prevent cancer recurrence","volume":"277","author":"Raghav","year":"2021","journal-title":"Life Sci."},{"key":"ref_35","doi-asserted-by":"crossref","first-page":"e157285","DOI":"10.1172\/jci.insight.157285","article-title":"Macrophage secretory IL-1\u03b2 promotes docetaxel resistance in head and neck squamous carcinoma via SOD2\/CAT-ICAM1 signaling","volume":"7","author":"Hsieh","year":"2022","journal-title":"JCI Insight"},{"key":"ref_36","doi-asserted-by":"crossref","unstructured":"Leung, E.L., Fiscus, R.R., Tung, J.W., Tin, V.P., Cheng, L.C., Sihoe, A.D., Fink, L.M., Ma, Y., and Wong, M.P. (2010). Non-small cell lung cancer cells expressing CD44 are enriched for stem cell-like properties. PLoS ONE, 5.","DOI":"10.1371\/journal.pone.0014062"},{"key":"ref_37","doi-asserted-by":"crossref","unstructured":"Zakaria, N., Yusoff, N.M., Zakaria, Z., Lim, M.N., Baharuddin, P.J., Fakiruddin, K.S., and Yahaya, B. (2015). Human non-small cell lung cancer expresses putative cancer stem cell markers and exhibits the transcriptomic profile of multipotent cells. BMC Cancer, 15.","DOI":"10.1186\/s12885-015-1086-3"},{"key":"ref_38","doi-asserted-by":"crossref","first-page":"1474","DOI":"10.1126\/science.146.3650.1474","article-title":"Cycloheximide: Aspects of inhibition of protein synthesis in mammalian cells","volume":"146","author":"Ennis","year":"1964","journal-title":"Science"},{"key":"ref_39","doi-asserted-by":"crossref","first-page":"1","DOI":"10.1016\/j.bcp.2015.12.006","article-title":"Targeting transcription factors by small compounds-Current strategies and future implications","volume":"107","author":"Hagenbuchner","year":"2016","journal-title":"Biochem. Pharmacol."},{"key":"ref_40","doi-asserted-by":"crossref","first-page":"2100","DOI":"10.1038\/nprot.2014.138","article-title":"The cellular thermal shift assay for evaluating drug target interactions in cells","volume":"9","author":"Jafari","year":"2014","journal-title":"Nat. Protoc."},{"key":"ref_41","doi-asserted-by":"crossref","first-page":"1623","DOI":"10.1016\/j.mayocp.2019.01.013","article-title":"Non-Small Cell Lung Cancer: Epidemiology, Screening, Diagnosis, and Treatment","volume":"94","author":"Duma","year":"2019","journal-title":"Mayo Clin. Proc."},{"key":"ref_42","doi-asserted-by":"crossref","first-page":"3552","DOI":"10.1200\/JCO.2007.13.9030","article-title":"Lung adjuvant cisplatin evaluation: A pooled analysis by the LACE Collaborative Group","volume":"26","author":"Pignon","year":"2008","journal-title":"J. Clin. Oncol."},{"key":"ref_43","doi-asserted-by":"crossref","first-page":"446","DOI":"10.1038\/nature22364","article-title":"Phylogenetic ctDNA analysis depicts early-stage lung cancer evolution","volume":"545","author":"Abbosh","year":"2017","journal-title":"Nature"},{"key":"ref_44","doi-asserted-by":"crossref","first-page":"708","DOI":"10.1002\/cncr.33985","article-title":"Perioperative circulating tumor DNA as a potential prognostic marker for operable stage I to IIIA non-small cell lung cancer","volume":"128","author":"Li","year":"2022","journal-title":"Cancer"},{"key":"ref_45","doi-asserted-by":"crossref","first-page":"82","DOI":"10.1016\/j.lungcan.2016.09.005","article-title":"Prediction of distant recurrence in resected stage I and II lung adenocarcinoma","volume":"101","author":"Aramini","year":"2016","journal-title":"Lung Cancer"},{"key":"ref_46","doi-asserted-by":"crossref","first-page":"1529","DOI":"10.1001\/jamaoncol.2017.1609","article-title":"Development and Validation of an Individualized Immune Prognostic Signature in Early-Stage Nonsquamous Non-Small Cell Lung Cancer","volume":"3","author":"Li","year":"2017","journal-title":"JAMA Oncol."},{"key":"ref_47","doi-asserted-by":"crossref","first-page":"798","DOI":"10.1007\/s12094-015-1440-6","article-title":"Prognostic value of ERCC1, RRM1, BRCA1 and SETDB1 in early stage of non-small cell lung cancer","volume":"18","author":"Galbis","year":"2016","journal-title":"Clin. Transl. Oncol."},{"key":"ref_48","doi-asserted-by":"crossref","first-page":"e533","DOI":"10.1016\/j.cllc.2018.04.004","article-title":"ADAURA: Phase III, Double-blind, Randomized Study of Osimertinib Versus Placebo in EGFR Mutation-positive Early-stage NSCLC After Complete Surgical Resection","volume":"19","author":"Wu","year":"2018","journal-title":"Clin. Lung Cancer"},{"key":"ref_49","doi-asserted-by":"crossref","unstructured":"Mamdani, H., Matosevic, S., Khalid, A.B., Durm, G., and Jalal, S.I. (2022). Immunotherapy in Lung Cancer: Current Landscape and Future Directions. Front. Immunol., 13.","DOI":"10.3389\/fimmu.2022.823618"},{"key":"ref_50","doi-asserted-by":"crossref","first-page":"664","DOI":"10.1038\/s41571-023-00794-7","article-title":"Immune-checkpoint inhibition for resectable non-small-cell lung cancer\u2014Opportunities and challenges","volume":"20","author":"Mountzios","year":"2023","journal-title":"Nat. Rev. Clin. Oncol."},{"key":"ref_51","doi-asserted-by":"crossref","first-page":"385","DOI":"10.1016\/j.lungcan.2004.08.016","article-title":"Compliance with post-operative adjuvant chemotherapy in non-small cell lung cancer. An analysis of National Cancer Institute of Canada and intergroup trial JBR.10 and a review of the literature","volume":"47","author":"Alam","year":"2005","journal-title":"Lung Cancer"},{"key":"ref_52","doi-asserted-by":"crossref","first-page":"2589","DOI":"10.1056\/NEJMoa043623","article-title":"Vinorelbine plus cisplatin vs. observation in resected non-small-cell lung cancer","volume":"352","author":"Winton","year":"2005","journal-title":"N. Engl. J. Med."},{"key":"ref_53","doi-asserted-by":"crossref","first-page":"1938","DOI":"10.1016\/S0140-6736(08)61354-9","article-title":"Traditional Chinese medicine","volume":"372","author":"Tang","year":"2008","journal-title":"Lancet"},{"key":"ref_54","doi-asserted-by":"crossref","unstructured":"Li, Z., Feiyue, Z., and Gaofeng, L. (2021). Traditional Chinese medicine and lung cancer-From theory to practice. Biomed. Pharmacother., 137.","DOI":"10.1016\/j.biopha.2021.111381"},{"key":"ref_55","doi-asserted-by":"crossref","first-page":"4369027","DOI":"10.1155\/2018\/4369027","article-title":"Traditional Chinese Medicine Integrated with Chemotherapy for Stage II-IIIA Patients with Non-Small-Cell Lung Cancer after Radical Surgery: A Retrospective Clinical Analysis with Small Sample Size","volume":"2018","author":"Zhao","year":"2018","journal-title":"Evid. Based Complement. Alternat. Med."},{"key":"ref_56","doi-asserted-by":"crossref","first-page":"812","DOI":"10.1007\/s11655-019-3168-6","article-title":"Association between Chinese Medicine Therapy and Survival Outcomes in Postoperative Patients with NSCLC: A Multicenter, Prospective, Cohort Study","volume":"25","author":"Wang","year":"2019","journal-title":"Chin. J. Integr. Med."},{"key":"ref_57","doi-asserted-by":"crossref","first-page":"506","DOI":"10.1111\/cpr.12143","article-title":"Plant natural products: From traditional compounds to new emerging drugs in cancer therapy","volume":"47","author":"Ouyang","year":"2014","journal-title":"Cell Prolif."},{"key":"ref_58","doi-asserted-by":"crossref","first-page":"902","DOI":"10.1111\/cas.12679","article-title":"Celastrol induces proteasomal degradation of FANCD2 to sensitize lung cancer cells to DNA crosslinking agents","volume":"106","author":"Wang","year":"2015","journal-title":"Cancer Sci."},{"key":"ref_59","doi-asserted-by":"crossref","first-page":"3591","DOI":"10.1007\/s13277-014-2996-4","article-title":"Curcumin reverses cisplatin resistance in cisplatin-resistant lung caner cells by inhibiting FA\/BRCA pathway","volume":"36","author":"Chen","year":"2015","journal-title":"Tumour Biol."},{"key":"ref_60","doi-asserted-by":"crossref","first-page":"113","DOI":"10.1021\/ml400341k","article-title":"Ethoxysanguinarine Induces Inhibitory Effects and Downregulates CIP2A in Lung Cancer Cells","volume":"5","author":"Liu","year":"2013","journal-title":"ACS Med. Chem. Lett."},{"key":"ref_61","doi-asserted-by":"crossref","first-page":"707","DOI":"10.3892\/etm.2013.889","article-title":"Combined anticancer activity of osthole and cisplatin in NCI-H460 lung cancer cells in vitro","volume":"5","author":"Xu","year":"2013","journal-title":"Exp. Ther. Med."},{"key":"ref_62","doi-asserted-by":"crossref","first-page":"843","DOI":"10.3892\/ijo.2015.3304","article-title":"Phloretin exhibits an anticancer effect and enhances the anticancer ability of cisplatin on non-small cell lung cancer cell lines by regulating expression of apoptotic pathways and matrix metalloproteinases","volume":"48","author":"Ma","year":"2016","journal-title":"Int. J. Oncol."},{"key":"ref_63","doi-asserted-by":"crossref","first-page":"1460","DOI":"10.3892\/ijo.2015.3124","article-title":"Resveratrol enhanced anticancer effects of cisplatin on non-small cell lung cancer cell lines by inducing mitochondrial dysfunction and cell apoptosis","volume":"47","author":"Ma","year":"2015","journal-title":"Int. J. Oncol."},{"key":"ref_64","doi-asserted-by":"crossref","unstructured":"Li, B., Chen, J., He, J., Peng, J., Wang, Y., Liu, S., and Jiang, Y. (2023). Total alkaloids in Stephania tetrandra induce apoptosis by regulating BBC3 in human non-small cell lung cancer cells. Biomed. Pharmacother., 162.","DOI":"10.1016\/j.biopha.2023.114635"},{"key":"ref_65","doi-asserted-by":"crossref","first-page":"125","DOI":"10.1142\/S0192415X06003692","article-title":"Antiproliferative and apoptotic effects of tetrandrine on different human hepatoma cell lines","volume":"34","author":"Ng","year":"2006","journal-title":"Am. J. Chin. Med."},{"key":"ref_66","doi-asserted-by":"crossref","first-page":"360","DOI":"10.3892\/ijo.2014.2735","article-title":"Tetrandrine induces G1\/S cell cycle arrest through the ROS\/Akt pathway in EOMA cells and inhibits angiogenesis in vivo","volume":"46","author":"Xiao","year":"2015","journal-title":"Int. J. Oncol."},{"key":"ref_67","doi-asserted-by":"crossref","first-page":"395","DOI":"10.1002\/tox.22053","article-title":"Tetrandrine induces apoptosis Via caspase-8, -9, and -3 and poly (ADP ribose) polymerase dependent pathways and autophagy through beclin-1\/ LC3-I, II signaling pathways in human oral cancer HSC-3 cells","volume":"31","author":"Yu","year":"2016","journal-title":"Environ. Toxicol."},{"key":"ref_68","doi-asserted-by":"crossref","first-page":"1790","DOI":"10.1002\/ptr.4936","article-title":"Fangchinoline induces G1 arrest in breast cancer cells through cell-cycle regulation","volume":"27","author":"Xing","year":"2013","journal-title":"Phytother. Res."},{"key":"ref_69","doi-asserted-by":"crossref","first-page":"111898","DOI":"10.1016\/j.ejmech.2019.111898","article-title":"Fangchinoline derivatives induce cell cycle arrest and apoptosis in human leukemia cell lines via suppression of the PI3K\/AKT and MAPK signaling pathway","volume":"186","author":"Yang","year":"2020","journal-title":"Eur. J. Med. Chem."},{"key":"ref_70","doi-asserted-by":"crossref","first-page":"40","DOI":"10.1186\/s12935-017-0410-1","article-title":"The effect of tetrandrine combined with cisplatin on proliferation and apoptosis of A549\/DDP cells and A549 cells","volume":"17","author":"Ye","year":"2017","journal-title":"Cancer Cell Int."},{"key":"ref_71","doi-asserted-by":"crossref","first-page":"116679","DOI":"10.1016\/j.taap.2023.116679","article-title":"Identification of Fangchinoline as a novel autophagy inhibitor with an adjuvant of chemotherapy against lung cancer","volume":"477","author":"Ren","year":"2023","journal-title":"Toxicol. Appl. Pharmacol."},{"key":"ref_72","doi-asserted-by":"crossref","first-page":"268","DOI":"10.1016\/j.ejmech.2019.05.027","article-title":"Natural products as multidrug resistance modulators in cancer","volume":"176","author":"Kumar","year":"2019","journal-title":"Eur. J. Med. Chem."},{"key":"ref_73","doi-asserted-by":"crossref","unstructured":"Matada, B.S., Pattanashettar, R., and Yernale, N.G. (2021). A comprehensive review on the biological interest of quinoline and its derivatives. Bioorg. Med. Chem., 32.","DOI":"10.1016\/j.bmc.2020.115973"},{"key":"ref_74","doi-asserted-by":"crossref","first-page":"104168","DOI":"10.1016\/j.arabjc.2022.104168","article-title":"Review on recent development of quinoline for anticancer activities","volume":"15","author":"Ilakiyalakshmi","year":"2022","journal-title":"Arab. J. Chem."},{"key":"ref_75","doi-asserted-by":"crossref","unstructured":"Olofinsan, K., Abrahamse, H., and George, B.P. (2023). Therapeutic Role of Alkaloids and Alkaloid Derivatives in Cancer Management. Molecules, 28.","DOI":"10.3390\/molecules28145578"},{"key":"ref_76","doi-asserted-by":"crossref","unstructured":"Zhang, H., Shangguan, F., Zhang, L., Ma, N., Song, S., Ma, L., Liu, C., Liu, M., An, J., and Li, H. (2023). A novel mechanism of 6-methoxydihydroavicine in suppressing ovarian carcinoma by disrupting mitochondrial homeostasis and triggering ROS\/MAPK mediated apoptosis. Front. Pharmacol., 14.","DOI":"10.3389\/fphar.2023.1093650"},{"key":"ref_77","doi-asserted-by":"crossref","first-page":"385","DOI":"10.1016\/j.jpha.2020.03.003","article-title":"Comparative pharmacokinetics of six major compounds in normal and insomnia rats after oral administration of Ziziphi Spinosae Semen aqueous extract","volume":"10","author":"Du","year":"2020","journal-title":"J. Pharm. Anal."},{"key":"ref_78","doi-asserted-by":"crossref","first-page":"231","DOI":"10.1016\/j.jare.2023.11.003","article-title":"Natural aporphine alkaloids: A comprehensive review of phytochemistry, pharmacokinetics, anticancer activities, and clinical application","volume":"63","author":"Sun","year":"2024","journal-title":"J. Adv. Res."},{"key":"ref_79","doi-asserted-by":"crossref","unstructured":"Lugones, Y., Loren, P., and Salazar, L.A. (2022). Cisplatin Resistance: Genetic and Epigenetic Factors Involved. Biomolecules, 12.","DOI":"10.3390\/biom12101365"},{"key":"ref_80","doi-asserted-by":"crossref","first-page":"15","DOI":"10.2174\/1568011053352587","article-title":"Cisplatin resistance and transcription factors","volume":"5","author":"Torigoe","year":"2005","journal-title":"Curr. Med. Chem. Anticancer Agents"},{"key":"ref_81","doi-asserted-by":"crossref","unstructured":"Sun, P., Song, Y., Liu, D., Liu, G., Mao, X., Dong, B., Braicu, E.I., and Sehouli, J. (2018). Potential role of the HOXD8 transcription factor in cisplatin resistance and tumour metastasis in advanced epithelial ovarian cancer. Sci. Rep., 8.","DOI":"10.1038\/s41598-018-31030-3"},{"key":"ref_82","first-page":"1083","article-title":"Epigenetic activation of FOXF1 confers cancer stem cell properties to cisplatin-resistant non-small cell lung cancer","volume":"56","author":"Zhao","year":"2020","journal-title":"Int. J. Oncol."},{"key":"ref_83","doi-asserted-by":"crossref","first-page":"175728","DOI":"10.1016\/j.ejphar.2023.175728","article-title":"Trichostatin A inhibits expression of the human SLC2A5 gene via SNAI1\/SNAI2 transcription factors and sensitizes colon cancer cells to platinum compounds","volume":"949","author":"Karwaciak","year":"2023","journal-title":"Eur. J. Pharmacol."},{"key":"ref_84","doi-asserted-by":"crossref","first-page":"4558","DOI":"10.1242\/dev.112672","article-title":"Fox transcription factors: From development to disease","volume":"143","author":"Golson","year":"2016","journal-title":"Development"},{"key":"ref_85","doi-asserted-by":"crossref","first-page":"eade2441","DOI":"10.1126\/sciadv.ade2441","article-title":"FOXG1 drives transcriptomic networks to specify principal neuron subtypes during the development of the medial pallium","volume":"9","author":"Ba","year":"2023","journal-title":"Sci. Adv."},{"key":"ref_86","doi-asserted-by":"crossref","first-page":"2956","DOI":"10.1038\/ncomms3956","article-title":"Transcription factors FOXG1 and Groucho\/TLE promote glioblastoma growth","volume":"4","author":"Verginelli","year":"2013","journal-title":"Nat. Commun."},{"key":"ref_87","doi-asserted-by":"crossref","first-page":"1113","DOI":"10.1210\/me.2012-1353","article-title":"Transcriptional repression of AIB1 by FoxG1 leads to apoptosis in breast cancer cells","volume":"27","author":"Li","year":"2013","journal-title":"Mol. Endocrinol."},{"key":"ref_88","doi-asserted-by":"crossref","first-page":"400","DOI":"10.1016\/j.humpath.2006.09.003","article-title":"FOXG1 is overexpressed in hepatoblastoma","volume":"38","author":"Adesina","year":"2007","journal-title":"Hum. Pathol."},{"key":"ref_89","doi-asserted-by":"crossref","first-page":"651","DOI":"10.3892\/mmr.2021.12290","article-title":"FOXG1 improves mitochondrial function and promotes the progression of nasopharyngeal carcinoma","volume":"24","author":"Xi","year":"2021","journal-title":"Mol. Med. Rep."},{"key":"ref_90","doi-asserted-by":"crossref","first-page":"e19540","DOI":"10.1016\/j.heliyon.2023.e19540","article-title":"FOXG1 regulates the proliferation and apoptosis of human lung cancer cells","volume":"9","author":"Chen","year":"2023","journal-title":"Heliyon"},{"key":"ref_91","doi-asserted-by":"crossref","first-page":"778","DOI":"10.7150\/jca.22282","article-title":"FOXG1 Expression Is Elevated in Glioma and Inhibits Glioma Cell Apoptosis","volume":"9","author":"Chen","year":"2018","journal-title":"J. Cancer"},{"key":"ref_92","doi-asserted-by":"crossref","first-page":"D1102","DOI":"10.1093\/nar\/gky1033","article-title":"PubChem 2019 update: Improved access to chemical data","volume":"47","author":"Kim","year":"2019","journal-title":"Nucleic Acids Res."}],"container-title":["Pharmaceuticals"],"original-title":[],"language":"en","link":[{"URL":"https:\/\/www.mdpi.com\/1424-8247\/17\/10\/1356\/pdf","content-type":"unspecified","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2025,10,10]],"date-time":"2025-10-10T16:11:02Z","timestamp":1760112662000},"score":1,"resource":{"primary":{"URL":"https:\/\/www.mdpi.com\/1424-8247\/17\/10\/1356"}},"subtitle":[],"short-title":[],"issued":{"date-parts":[[2024,10,11]]},"references-count":92,"journal-issue":{"issue":"10","published-online":{"date-parts":[[2024,10]]}},"alternative-id":["ph17101356"],"URL":"https:\/\/doi.org\/10.3390\/ph17101356","relation":{},"ISSN":["1424-8247"],"issn-type":[{"value":"1424-8247","type":"electronic"}],"subject":[],"published":{"date-parts":[[2024,10,11]]}}}