{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,5,16]],"date-time":"2026-05-16T00:52:42Z","timestamp":1778892762104,"version":"3.51.4"},"reference-count":43,"publisher":"MDPI AG","issue":"1","license":[{"start":{"date-parts":[[2024,1,9]],"date-time":"2024-01-09T00:00:00Z","timestamp":1704758400000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"funder":[{"name":"Lanzhou City Science and Technology Program","award":["2020-XG-36"],"award-info":[{"award-number":["2020-XG-36"]}]},{"name":"Lanzhou City Science and Technology Program","award":["(22)0660"],"award-info":[{"award-number":["(22)0660"]}]},{"name":"Lanzhou City Science and Technology Program","award":["lzukqky-2022-t12"],"award-info":[{"award-number":["lzukqky-2022-t12"]}]},{"name":"Lanzhou City Science and Technology Program","award":["lzukqky-2022-t16"],"award-info":[{"award-number":["lzukqky-2022-t16"]}]},{"name":"Fundamental Research Funds for the scientific research fund of the School (Hospital) of Stomatology Lanzhou University","award":["2020-XG-36"],"award-info":[{"award-number":["2020-XG-36"]}]},{"name":"Fundamental Research Funds for the scientific research fund of the School (Hospital) of Stomatology Lanzhou University","award":["(22)0660"],"award-info":[{"award-number":["(22)0660"]}]},{"name":"Fundamental Research Funds for the scientific research fund of the School (Hospital) of Stomatology Lanzhou University","award":["lzukqky-2022-t12"],"award-info":[{"award-number":["lzukqky-2022-t12"]}]},{"name":"Fundamental Research Funds for the scientific research fund of the School (Hospital) of Stomatology Lanzhou University","award":["lzukqky-2022-t16"],"award-info":[{"award-number":["lzukqky-2022-t16"]}]}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":["CIMB"],"abstract":"<jats:p>Isocorydine (ICD) exhibits strong antitumor effects on numerous human cell lines. However, the anticancer activity of ICD against oral squamous cell carcinoma (OSCC) has not been reported. The anticancer activity, migration and invasion ability, and changes in the cytoskeleton morphology and mechanical properties of ICD in OSCC were determined. Changes in the contents of reactive oxygen species (ROS), the mitochondrial membrane potential (MMP), ATP, and mitochondrial respiratory chain complex enzymes \u2160\u2013\u2163 in cancer cells were studied. ICD significantly inhibited the proliferation of oral tongue squamous cells (Cal-27), with an IC50 of 0.61 mM after 24 h of treatment. The invasion, migration, and adhesion of cancer cells were decreased, and cytoskeletal actin was deformed and depolymerized. In comparison to an untreated group, the activities of mitochondrial respiratory chain complex enzymes I-IV were significantly decreased by 50.72%, 27.39%, 77.27%, and 73.89%, respectively. The ROS production increased, the MMP decreased by 43.65%, and the ATP content decreased to 17.1 \u00b1 0.001 (mmol\/mL); ultimately, the apoptosis rate of cancer cells increased up to 10.57% after 24 h of action. These findings suggest that ICD exerted an obvious anticancer activity against OSCC and may inhibit Cal-27 proliferation and growth by causing mitochondrial dysfunction and interrupting cellular energy.<\/jats:p>","DOI":"10.3390\/cimb46010042","type":"journal-article","created":{"date-parts":[[2024,1,10]],"date-time":"2024-01-10T09:39:57Z","timestamp":1704879597000},"page":"650-662","update-policy":"https:\/\/doi.org\/10.3390\/mdpi_crossmark_policy","source":"Crossref","is-referenced-by-count":3,"title":["Isocorydine Exerts Anticancer Activity by Disrupting the Energy Metabolism and Filamentous Actin Structures of Oral Squamous Carcinoma Cells"],"prefix":"10.3390","volume":"46","author":[{"given":"Qiaozhen","family":"Zhou","sequence":"first","affiliation":[{"name":"Department (Hospital) of Stomatology, Lanzhou University, Lanzhou 730000, China"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Qianqian","family":"Zhang","sequence":"additional","affiliation":[{"name":"Department (Hospital) of Stomatology, Lanzhou University, Lanzhou 730000, China"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"ORCID":"https:\/\/orcid.org\/0009-0001-4059-5710","authenticated-orcid":false,"given":"Lingzi","family":"Liao","sequence":"additional","affiliation":[{"name":"Department (Hospital) of Stomatology, Lanzhou University, Lanzhou 730000, China"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Qian","family":"Li","sequence":"additional","affiliation":[{"name":"Department (Hospital) of Stomatology, Lanzhou University, Lanzhou 730000, China"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Huidan","family":"Qu","sequence":"additional","affiliation":[{"name":"Department (Hospital) of Stomatology, Lanzhou University, Lanzhou 730000, China"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Xinyu","family":"Wang","sequence":"additional","affiliation":[{"name":"Department (Hospital) of Stomatology, Lanzhou University, Lanzhou 730000, China"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Ying","family":"Zhou","sequence":"additional","affiliation":[{"name":"Department (Hospital) of Stomatology, Lanzhou University, Lanzhou 730000, China"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Guangzeng","family":"Zhang","sequence":"additional","affiliation":[{"name":"Department (Hospital) of Stomatology, Lanzhou University, Lanzhou 730000, China"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Mingliang","family":"Sun","sequence":"additional","affiliation":[{"name":"Department (Hospital) of Stomatology, Lanzhou University, Lanzhou 730000, China"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Kailiang","family":"Zhang","sequence":"additional","affiliation":[{"name":"Department (Hospital) of Stomatology, Lanzhou University, Lanzhou 730000, China"},{"name":"Key Laboratory of Dental Maxillofacial Reconstruction and Biological Intelligence Manufacturing, Lanzhou University, Lanzhou 730000, China"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Baoping","family":"Zhang","sequence":"additional","affiliation":[{"name":"Department (Hospital) of Stomatology, Lanzhou University, Lanzhou 730000, China"},{"name":"Key Laboratory of Dental Maxillofacial Reconstruction and Biological Intelligence Manufacturing, Lanzhou University, Lanzhou 730000, China"}],"role":[{"role":"author","vocabulary":"crossref"}]}],"member":"1968","published-online":{"date-parts":[[2024,1,9]]},"reference":[{"key":"ref_1","doi-asserted-by":"crossref","unstructured":"Imbesi Bellantoni, M., Picciolo, G., Pirrotta, I., Irrera, N., Vaccaro, M., Vaccaro, F., Squadrito, F., and Pallio, G. (2023). Oral Cavity Squamous Cell Carcinoma: An Update of the Pharmacological Treatment. Biomedicines, 11.","DOI":"10.3390\/biomedicines11041112"},{"key":"ref_2","doi-asserted-by":"crossref","first-page":"104348","DOI":"10.1016\/j.oraloncology.2019.06.029","article-title":"Tongue cancer: A discrete oral cavity subsite","volume":"99","author":"Shetty","year":"2019","journal-title":"Oral Oncol."},{"key":"ref_3","doi-asserted-by":"crossref","first-page":"821","DOI":"10.1002\/hed.25466","article-title":"Classification of GLOSSECTOMIES: Proposal for tongue cancer resections","volume":"41","author":"Ansarin","year":"2019","journal-title":"Head Neck"},{"key":"ref_4","doi-asserted-by":"crossref","unstructured":"Navarro-Orcajada, S., Vidal-S\u00e1nchez, F.J., Conesa, I., Escribano-Naharro, F., Matencio, A., and L\u00f3pez-Nicol\u00e1s, J.M. (2023). Antiproliferative Effects in Colorectal Cancer and Stabilisation in Cyclodextrins of the Phytoalexin Isorhapontigenin. Biomedicines, 11.","DOI":"10.3390\/biomedicines11113023"},{"key":"ref_5","doi-asserted-by":"crossref","unstructured":"Yang, D., Zhang, H., Wu, J., Ma, R., Li, Z., Wang, K., and Yang, F. (2019). The role of chamaejasmine in cellular apoptosis and autophagy in MG-63 cells. Biosci. Rep., 39.","DOI":"10.1042\/BSR20181707"},{"key":"ref_6","doi-asserted-by":"crossref","unstructured":"Huang, C., and Hu, G. (2018). Shikonin suppresses proliferation and induces apoptosis in endometrioid endometrial cancer cells via modulating miR-106b\/PTEN\/AKT\/mTOR signaling pathway. Biosci. Rep., 38.","DOI":"10.1042\/BSR20171546"},{"key":"ref_7","doi-asserted-by":"crossref","first-page":"1066280","DOI":"10.3389\/fchem.2023.1066280","article-title":"Recent advances in oridonin derivatives with anticancer activity","volume":"11","author":"Sobral","year":"2023","journal-title":"Front. Chem."},{"key":"ref_8","doi-asserted-by":"crossref","unstructured":"Nowak, P., Bil-Lula, I., and \u015aliwi\u0144ska-Mosso\u0144, M. (2023). A Cross-Talk about Radioresistance in Lung Cancer-How to Improve Radiosensitivity According to Chinese Medicine and Medicaments That Commonly Occur in Pharmacies. Int. J. Mol. Sci., 24.","DOI":"10.3390\/ijms241311206"},{"key":"ref_9","doi-asserted-by":"crossref","first-page":"2865","DOI":"10.1002\/jcb.25937","article-title":"Neferine Potentiates the Antitumor Effect of Cisplatin in Human Lung Adenocarcinoma Cells via a Mitochondria-Mediated Apoptosis Pathway","volume":"118","author":"Sivalingam","year":"2017","journal-title":"J. Cell. Biochem."},{"key":"ref_10","doi-asserted-by":"crossref","first-page":"568436","DOI":"10.3389\/fendo.2020.568436","article-title":"Sodium Danshensu Inhibits Oral Cancer Cell Migration and Invasion by Modulating p38 Signaling Pathway","volume":"11","author":"Kumar","year":"2020","journal-title":"Front. Endocrinol."},{"key":"ref_11","doi-asserted-by":"crossref","unstructured":"Kwak, A.W., Lee, M.H., Yoon, G., Cho, S.S., Choi, J.S., Chae, J.I., and Shim, J.H. (2020). Deoxypodophyllotoxin, a Lignan from Anthriscus sylvestris, Induces Apoptosis and Cell Cycle Arrest by Inhibiting the EGFR Signaling Pathways in Esophageal Squamous Cell Carcinoma Cells. Int. J. Mol. Sci., 21.","DOI":"10.3390\/ijms21186854"},{"key":"ref_12","doi-asserted-by":"crossref","first-page":"121","DOI":"10.1016\/j.jep.2009.02.013","article-title":"Caspase and mitogen activated protein kinase pathways are involved in Solanum lyratum herba induced apoptosis","volume":"123","author":"Lee","year":"2009","journal-title":"J. Ethnopharmacol."},{"key":"ref_13","doi-asserted-by":"crossref","first-page":"1148","DOI":"10.3892\/ijo.2012.1544","article-title":"Antitumor efficacy of sequential treatment with docetaxel and 5-fluorouracil against human oral cancer cells","volume":"41","author":"Tamatani","year":"2012","journal-title":"Int. J. Oncol."},{"key":"ref_14","doi-asserted-by":"crossref","unstructured":"Mousavi, S.M., Hashemi, S.A., Fallahi, N.F., Binazadeh, M., Dehdashtijahromi, M., Omidifar, N., Ghahramani, Y., Lai, C.W., Chiang, W.H., and Gholami, A. (2023). Innovative Metal-Organic Frameworks for Targeted Oral Cancer Therapy: A Review. Materials, 16.","DOI":"10.3390\/ma16134685"},{"key":"ref_15","doi-asserted-by":"crossref","first-page":"1638","DOI":"10.1021\/np000144r","article-title":"In Vitro antiplasmodial, antiamoebic, and cytotoxic activities of some monomeric isoquinoline alkaloids","volume":"63","author":"Wright","year":"2000","journal-title":"J. Nat. Prod."},{"key":"ref_16","first-page":"105","article-title":"Glaucium flavum crantz bitkisinden elde edilen bazi alkaloidlerin antibakteriyel etkileri [The antibacterial effects of some alkaloids isolated from Glaucium flavum Crantz]","volume":"15","author":"Bilgehan","year":"1981","journal-title":"Mikrobiyol. Bul."},{"key":"ref_17","doi-asserted-by":"crossref","unstructured":"Wang, H., Cheng, X., Kong, S., Yang, Z., Wang, H., Huang, Q., Li, J., Chen, C., and Ma, Y. (2016). Synthesis and Structure-Activity Relationships of a Series of Aporphine Derivatives with Antiarrhythmic Activities and Acute Toxicity. Molecules, 21.","DOI":"10.20944\/preprints201611.0072.v1"},{"key":"ref_18","doi-asserted-by":"crossref","first-page":"23533","DOI":"10.3390\/ijms141223533","article-title":"Identification and quantification of the main active anticancer alkaloids from the root of Glaucium flavum","volume":"14","author":"Bournine","year":"2013","journal-title":"Int. J. Mol. Sci."},{"key":"ref_19","doi-asserted-by":"crossref","first-page":"666","DOI":"10.1016\/j.fitote.2011.02.005","article-title":"Anti-ulcer constituents of Annona squamosa twigs","volume":"82","author":"Yadav","year":"2011","journal-title":"Fitoterapia"},{"key":"ref_20","doi-asserted-by":"crossref","unstructured":"Machado, T.Q., Lima, M.E.D., da Silva, R.C., Macedo, A.L., de Queiroz, L.N., Angrisani, B.R.P., da Fonseca, A.C.C., C\u00e2mara, P.R., Rabelo, V.V., and Carollo, C.A. (2023). Anticancer Activity and Molecular Targets of Piper cernuum Substances in Oral Squamous Cell Carcinoma Models. Biomedicines, 11.","DOI":"10.3390\/biomedicines11071914"},{"key":"ref_21","doi-asserted-by":"crossref","first-page":"21517","DOI":"10.1038\/srep21517","article-title":"Ultraviolet-visible study on acid-base equilibria of aporphine alkaloids with antiplasmodial and antioxidant activities from Alseodaphne corneri and Dehaasia longipedicellata","volume":"6","author":"Zahari","year":"2016","journal-title":"Sci. Rep."},{"key":"ref_22","first-page":"3702","article-title":"Isocorydine decrease gemcitabine-resistance by inhibiting epithelial-mesenchymal transition via STAT3 in pancreatic cancer cells","volume":"12","author":"Zhang","year":"2020","journal-title":"Am. J. Transl. Res."},{"key":"ref_23","doi-asserted-by":"crossref","first-page":"5951","DOI":"10.1007\/s13277-015-4362-6","article-title":"Derivate isocorydine inhibits cell proliferation in hepatocellular carcinoma cell lines by inducing G2\/M cell cycle arrest and apoptosis","volume":"37","author":"Chen","year":"2016","journal-title":"Tumour. Biol."},{"key":"ref_24","doi-asserted-by":"crossref","first-page":"25149","DOI":"10.18632\/oncotarget.4438","article-title":"An isocorydine derivative (d-ICD) inhibits drug resistance by downregulating IGF2BP3 expression in hepatocellular carcinoma","volume":"6","author":"Li","year":"2015","journal-title":"Oncotarget"},{"key":"ref_25","doi-asserted-by":"crossref","unstructured":"Liu, X., Tian, H., Li, H., Ge, C., Zhao, F., Yao, M., and Li, J. (2017). Derivate Isocorydine (d-ICD) Suppresses Migration and Invasion of Hepatocellular Carcinoma Cell by Downregulating ITGA1 Expression. Int. J. Mol. Sci., 18.","DOI":"10.3390\/ijms18030514"},{"key":"ref_26","doi-asserted-by":"crossref","first-page":"1136","DOI":"10.2119\/molmed.2012.00055","article-title":"Isocorydine targets the drug-resistant cellular side population through PDCD4-related apoptosis in hepatocellular carcinoma","volume":"18","author":"Lu","year":"2012","journal-title":"Mol. Med."},{"key":"ref_27","first-page":"154","article-title":"Isocorydine suppresses doxorubicin-induced epithelial-mesenchymal transition via inhibition of ERK signaling pathways in hepatocellular carcinoma","volume":"8","author":"Pan","year":"2018","journal-title":"Am. J. Cancer Res."},{"key":"ref_28","doi-asserted-by":"crossref","first-page":"912","DOI":"10.1080\/09553002.2019.1589653","article-title":"The Warburg effect: Essential part of metabolic reprogramming and central contributor to cancer progression","volume":"95","author":"Vaupel","year":"2019","journal-title":"Int. J. Radiat. Biol."},{"key":"ref_29","doi-asserted-by":"crossref","first-page":"330","DOI":"10.1007\/s10930-019-09819-6","article-title":"Transport of Proteins into Mitochondria","volume":"38","author":"Hansen","year":"2019","journal-title":"Protein. J."},{"key":"ref_30","doi-asserted-by":"crossref","unstructured":"Rochette, L., Meloux, A., Zeller, M., Malka, G., Cottin, Y., and Vergely, C. (2020). Mitochondrial SLC25 Carriers: Novel Targets for Cancer Therapy. Molecules, 25.","DOI":"10.3390\/molecules25102417"},{"key":"ref_31","doi-asserted-by":"crossref","first-page":"11","DOI":"10.5483\/BMBRep.2008.41.1.011","article-title":"The role of mitochondria in apoptosis","volume":"41","author":"Eong","year":"2008","journal-title":"BMB Rep."},{"key":"ref_32","doi-asserted-by":"crossref","unstructured":"Majiene, D., Kuseliauskyte, J., Stimbirys, A., and Jekabsone, A. (2019). Comparison of the Effect of Native 1,4-Naphthoquinones Plumbagin, Menadione, and Lawsone on Viability, Redox Status, and Mitochondrial Functions of C6 Glioblastoma Cells. Nutrients, 11.","DOI":"10.3390\/nu11061294"},{"key":"ref_33","doi-asserted-by":"crossref","first-page":"11692","DOI":"10.1038\/srep11692","article-title":"Fast, multi-frequency, and quantitative nanomechanical mapping of live cells using the atomic force microscope","volume":"5","author":"Wang","year":"2015","journal-title":"Sci. Rep."},{"key":"ref_34","doi-asserted-by":"crossref","first-page":"29","DOI":"10.1038\/s41419-017-0044-1","article-title":"Dual suppression of inner and outer mitochondrial membrane functions augments apoptotic responses to oncogenic MAPK inhibition","volume":"9","author":"Serasinghe","year":"2018","journal-title":"Cell Death Dis."},{"key":"ref_35","doi-asserted-by":"crossref","first-page":"7819","DOI":"10.1038\/srep07819","article-title":"Identification of molecular signature of head and neck cancer stem-like cells","volume":"5","author":"Shrivastava","year":"2015","journal-title":"Sci. Rep."},{"key":"ref_36","doi-asserted-by":"crossref","first-page":"236","DOI":"10.1038\/emboj.2011.343","article-title":"Three-dimensional reconstructions of Arp2\/3 complex with bound nucleation promoting factors","volume":"31","author":"Xu","year":"2012","journal-title":"EMBO J."},{"key":"ref_37","doi-asserted-by":"crossref","first-page":"2123","DOI":"10.1016\/j.bpj.2013.04.019","article-title":"Quantitative study of the elastic modulus of loosely attached cells in AFM indentation experiments","volume":"104","author":"Dokukin","year":"2013","journal-title":"Biophys. J."},{"key":"ref_38","doi-asserted-by":"crossref","first-page":"249","DOI":"10.1016\/j.trecan.2020.10.009","article-title":"3D In Vitro Model (R)evolution: Unveiling Tumor-Stroma Interactions","volume":"7","author":"Rodrigues","year":"2021","journal-title":"Trends. Cancer"},{"key":"ref_39","doi-asserted-by":"crossref","first-page":"3365","DOI":"10.1021\/acsnano.5b07162","article-title":"Effect of Actin Organization on the Stiffness of Living Breast Cancer Cells Revealed by Peak-Force Modulation Atomic Force Microscopy","volume":"10","author":"Encinar","year":"2016","journal-title":"ACS Nano"},{"key":"ref_40","doi-asserted-by":"crossref","first-page":"447","DOI":"10.1007\/s10555-022-10027-5","article-title":"Treatment against glucose-dependent cancers through metabolic PFKFB3 targeting of glycolytic flux","volume":"41","author":"Jones","year":"2022","journal-title":"Cancer Metastasis Rev."},{"key":"ref_41","doi-asserted-by":"crossref","unstructured":"Fukushi, A., Kim, H.D., Chang, Y.C., and Kim, C.H. (2022). Revisited Metabolic Control and Reprogramming Cancers by Means of the Warburg Effect in Tumor Cells. Int. J. Mol. Sci., 23.","DOI":"10.3390\/ijms231710037"},{"key":"ref_42","doi-asserted-by":"crossref","first-page":"2287","DOI":"10.1002\/jbmr.2584","article-title":"Alternative NF-\u03baB Regulates RANKL-Induced Osteoclast Differentiation and Mitochondrial Biogenesis via Independent Mechanisms","volume":"30","author":"Zeng","year":"2015","journal-title":"J. Bone Miner. Res."},{"key":"ref_43","doi-asserted-by":"crossref","first-page":"678","DOI":"10.1016\/j.bbabio.2010.01.011","article-title":"Structure-function relationships in feedback regulation of energy fluxes in vivo in health and disease: Mitochondrial interactosome","volume":"1797","author":"Saks","year":"2010","journal-title":"Biochim. Biophys. Acta"}],"container-title":["Current Issues in Molecular Biology"],"original-title":[],"language":"en","link":[{"URL":"https:\/\/www.mdpi.com\/1467-3045\/46\/1\/42\/pdf","content-type":"unspecified","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2025,10,10]],"date-time":"2025-10-10T13:43:09Z","timestamp":1760103789000},"score":1,"resource":{"primary":{"URL":"https:\/\/www.mdpi.com\/1467-3045\/46\/1\/42"}},"subtitle":[],"short-title":[],"issued":{"date-parts":[[2024,1,9]]},"references-count":43,"journal-issue":{"issue":"1","published-online":{"date-parts":[[2024,1]]}},"alternative-id":["cimb46010042"],"URL":"https:\/\/doi.org\/10.3390\/cimb46010042","relation":{},"ISSN":["1467-3045"],"issn-type":[{"value":"1467-3045","type":"electronic"}],"subject":[],"published":{"date-parts":[[2024,1,9]]}}}