{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,7,30]],"date-time":"2026-07-30T12:14:15Z","timestamp":1785413655232,"version":"3.56.0"},"reference-count":102,"publisher":"MDPI AG","issue":"14","license":[{"start":{"date-parts":[[2026,7,17]],"date-time":"2026-07-17T00:00:00Z","timestamp":1784246400000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"funder":[{"DOI":"10.13039\/501100004515","name":"Universiti Kebangsaan Malaysia","doi-asserted-by":"crossref","award":["DD-2023-014."],"award-info":[{"award-number":["DD-2023-014."]}],"id":[{"id":"10.13039\/501100004515","id-type":"DOI","asserted-by":"crossref"}]},{"award":["DD-2023-014."],"award-info":[{"award-number":["DD-2023-014."]}],"id":[{"id":"https:\/\/ror.org\/00bw8d226","id-type":"ROR","asserted-by":"publisher"}]}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":["IJMS"],"abstract":"<jats:p>Oral squamous cell carcinoma (OSCC) is the most common malignancy of the head and neck, with current treatments offering limited improvement in survival outcomes. This has driven interest in natural compounds as potential therapeutic alternatives. Cosmos caudatus (CC), commonly known as \u201culam raja,\u201d possesses antioxidant and anticancer properties, but its effects on OSCC remain insufficiently explored. This study aimed to evaluate the cytotoxic effects of CC extract and its impact on TP53\/p53 and CD44 expression in an OSCC cell line in vitro. Cells were characterised using immunocytochemistry (ICC) and treated with CC extract (10\u201380 mg\/mL). Cell viability was assessed using the MTT assay, while TP53 and CD44 gene expression were analysed via RT-qPCR. p53 protein levels were quantified using ELISA, and ICC was performed to assess protein expression. Results: CC demonstrated significant cytotoxicity with an IC50 of 58 mg\/mL (p &lt; 0.05). Treatment resulted in significant downregulation of TP53\/p53 at both gene and protein levels (p &lt; 0.05), alongside increased CD44 mRNA expression but reduced protein staining. CC may therefore have potential as a plant-derived adjunctive therapeutic agent, although further studies are required to elucidate its mechanisms and clinical applicability.<\/jats:p>","DOI":"10.3390\/ijms27146361","type":"journal-article","created":{"date-parts":[[2026,7,20]],"date-time":"2026-07-20T07:54:13Z","timestamp":1784534053000},"page":"6361","update-policy":"https:\/\/doi.org\/10.3390\/mdpi_crossmark_policy","source":"Crossref","is-referenced-by-count":0,"title":["Modulation of TP53 Expression by Cosmos caudatus (Ulam raja) in OSCC Cell Lines"],"prefix":"10.3390","volume":"27","author":[{"given":"Kelvin Sin-Hou","family":"Liaw","sequence":"first","affiliation":[{"name":"Department of Family Oral Health, Faculty of Dentistry, Universiti Kebangsaan Malaysia, Kuala Lumpur 50300, Malaysia"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-0200-086X","authenticated-orcid":false,"given":"Sook-Luan","family":"Ng","sequence":"additional","affiliation":[{"name":"Department of Craniofacial Diagnostics & Biosciences, Faculty of Dentistry, Universiti Kebangsaan Malaysia, Kuala Lumpur 50300, Malaysia"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-3720-8617","authenticated-orcid":false,"given":"Alida","family":"Mahyuddin","sequence":"additional","affiliation":[{"name":"Department of Family Oral Health, Faculty of Dentistry, Universiti Kebangsaan Malaysia, Kuala Lumpur 50300, Malaysia"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-2495-0468","authenticated-orcid":false,"given":"Norliwati","family":"Ibrahim","sequence":"additional","affiliation":[{"name":"Department of Craniofacial Diagnostics & Biosciences, Faculty of Dentistry, Universiti Kebangsaan Malaysia, Kuala Lumpur 50300, Malaysia"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Eng-Wee","family":"Chua","sequence":"additional","affiliation":[{"name":"Faculty of Pharmacy, Universiti Kebangsaan Malaysia, Kuala Lumpur 50300, Malaysia"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Yee Xing","family":"You","sequence":"additional","affiliation":[{"name":"Center for Healthy Aging & Wellness, Faculty of Health Sciences, Universiti Kebangsaan Malaysia, Kuala Lumpur 50300, Malaysia"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-7424-5938","authenticated-orcid":false,"given":"Nurul Inaas","family":"Mahamad Apandi","sequence":"additional","affiliation":[{"name":"Department of Craniofacial Diagnostics & Biosciences, Faculty of Dentistry, Universiti Kebangsaan Malaysia, Kuala Lumpur 50300, Malaysia"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"1968","published-online":{"date-parts":[[2026,7,17]]},"reference":[{"key":"ref_1","doi-asserted-by":"crossref","unstructured":"Mahboubi, K., Nakoneshny, S.C., Sauro, K., Roberts, S., Hart, R., Matthews, T.W., Dort, J., and Chandarana, S.P. (2024). The Association of Ethnicity and Oncologic Outcomes for Oral Cavity Squamous Cell Carcinoma (OSCC). Cancers, 16.","DOI":"10.1101\/2024.02.25.24303341"},{"key":"ref_2","unstructured":"Ferlay, J., Ervik, M., Lam, F., Laversanne, M., Colombet, M., Mery, L., Pi\u00f1eros, M., Znaor, A., Soerjomataram, I., and Bray, F. (2025, December 14). Global Cancer Observatory: Cancer Today. Available online: https:\/\/gco.iarc.who.int\/today."},{"key":"ref_3","doi-asserted-by":"crossref","unstructured":"Xu, Z., Xu, M., Sun, Z., Feng, Q., Xu, S., and Peng, H. (2025). A nomogram for predicting overall survival in oral squamous cell carcinoma: A SEER database and external validation study. Front. Oncol., 15.","DOI":"10.3389\/fonc.2025.1557459"},{"key":"ref_4","first-page":"e54394","article-title":"Comprehensive Analysis of Oral Squamous Cell Carcinomas: Clinical, Epidemiological, and Histopathological Insights with a Focus on Prognostic Factors and Survival Time","volume":"16","author":"Fatima","year":"2024","journal-title":"Cureus"},{"key":"ref_5","doi-asserted-by":"crossref","first-page":"e27127","DOI":"10.1097\/MD.0000000000027127","article-title":"Risk factors associated with the mortality rate of oral squamous cell carcinoma patients: A 10-year retrospective study","volume":"100","author":"Ahmad","year":"2021","journal-title":"Medicine"},{"key":"ref_6","doi-asserted-by":"crossref","unstructured":"Cabral, L.G.d.S., Martins, I.M., Paulo, E.P.d.A., Pomini, K.T., Poyet, J.-L., and Maria, D.A. (2025). Molecular Mechanisms in the Carcinogenesis of Oral Squamous Cell Carcinoma: A Literature Review. Biomolecules, 15.","DOI":"10.3390\/biom15050621"},{"key":"ref_7","doi-asserted-by":"crossref","unstructured":"Miranda-Galvis, M., Loveless, R., Kowalski, L.P., and Teng, Y. (2021). Impacts of Environmental Factors on Head and Neck Cancer Pathogenesis and Progression. Cells, 10.","DOI":"10.3390\/cells10020389"},{"key":"ref_8","doi-asserted-by":"crossref","first-page":"13","DOI":"10.33279\/jkcd.v15i01.787","article-title":"Knowledge about Role of HPV as a Risk Factor of Oral Squamous Cell Carcinoma amomg Dentists in Asia: A Systemic Review","volume":"15","author":"Ilyas","year":"2025","journal-title":"J. Khyber Coll. Dent."},{"key":"ref_9","doi-asserted-by":"crossref","first-page":"44","DOI":"10.1038\/s41368-023-00249-w","article-title":"Oral squamous cell carcinomas: State of the field and emerging directions","volume":"15","author":"Tan","year":"2023","journal-title":"Int. J. Oral. Sci."},{"key":"ref_10","doi-asserted-by":"crossref","first-page":"1310","DOI":"10.1002\/lary.29260","article-title":"Survival of Young Versus Old Patients with Oral Cavity Squamous Cell Carcinoma: A Meta-Analysis","volume":"131","author":"Lee","year":"2021","journal-title":"Laryngoscope"},{"key":"ref_11","doi-asserted-by":"crossref","unstructured":"Lenoci, D., Moresco, E., Cavalieri, S., Bergamini, C., Torchia, E., Botta, L., Canevari, S., Trama, A., Licitra, L., and De Cecco, L. (2024). Oral cancer in young adults: Incidence, risk factors, prognosis, and molecular biomarkers. Front. Oncol., 14.","DOI":"10.3389\/fonc.2024.1452909"},{"key":"ref_12","doi-asserted-by":"crossref","first-page":"150","DOI":"10.1007\/s00784-025-06213-8","article-title":"Unique clinical features and prognostic risk factors of oral squamous cell carcinoma in patients under 30 years old","volume":"29","author":"Cheng","year":"2025","journal-title":"Clin. Oral. Investig."},{"key":"ref_13","doi-asserted-by":"crossref","first-page":"19160216251351562","DOI":"10.1177\/19160216251351562","article-title":"Oral Cavity Squamous Cell Carcinoma in Young Patients: A Multi-Institutional Study of the Canadian Head & Neck Collaborative Research Initiative","volume":"54","author":"Hong","year":"2025","journal-title":"J. Otolaryngol.-Head Neck Surg."},{"key":"ref_14","doi-asserted-by":"crossref","first-page":"1099","DOI":"10.1007\/s12105-021-01320-w","article-title":"Clinicopathologic Characteristics of Young Patients with Oral Squamous Cell Carcinoma","volume":"15","author":"Mneimneh","year":"2021","journal-title":"Head Neck Pathol."},{"key":"ref_15","doi-asserted-by":"crossref","first-page":"4868","DOI":"10.1038\/s41598-023-32092-8","article-title":"Different impacts of TP53 mutations on cell cycle-related gene expression among cancer types","volume":"13","author":"Sasaki","year":"2023","journal-title":"Sci. Rep."},{"key":"ref_16","first-page":"e1401","article-title":"Correlation of TP53 Overexpression and Clinical Parameters with Five-Year Survival in Oral Squamous Cell Carcinoma Patients","volume":"9","author":"Ali","year":"2017","journal-title":"Cureus"},{"key":"ref_17","doi-asserted-by":"crossref","first-page":"582","DOI":"10.4103\/jomfp.JOMFP_106_20","article-title":"Expression of p53 at invasive front of oral squamous cell carcinoma and negative histopathological surgical margins to establish correlation at 3-year survival","volume":"24","author":"Gawande","year":"2020","journal-title":"J. Oral. Maxillofac. Pathol."},{"key":"ref_18","first-page":"1071","article-title":"p53: The guardian of genome against OSCC progression","volume":"7","author":"Puteri","year":"2020","journal-title":"Eur. J. Mol. Clin. Med."},{"key":"ref_19","doi-asserted-by":"crossref","first-page":"170","DOI":"10.1038\/s41392-024-01851-y","article-title":"Cancer stem cells: Advances in knowledge and implications for cancer therapy","volume":"9","author":"Chu","year":"2024","journal-title":"Signal Transduct. Target. Ther."},{"key":"ref_20","doi-asserted-by":"crossref","unstructured":"Shahoumi, L.A. (2021). Oral Cancer Stem Cells: Therapeutic Implications and Challenges. Front. Oral. Health, 2.","DOI":"10.3389\/froh.2021.685236"},{"key":"ref_21","doi-asserted-by":"crossref","first-page":"158","DOI":"10.4103\/crst.crst_97_23","article-title":"Correlation of prognosis of oral squamous cell carcinoma with CD44 expression: A retrospective immunohistochemical analysis","volume":"7","author":"Vasanthi","year":"2024","journal-title":"Cancer Res. Stat. Treat."},{"key":"ref_22","doi-asserted-by":"crossref","first-page":"109","DOI":"10.1007\/s12070-022-03200-3","article-title":"Over Expression of Cancer Stem Cell Marker CD44 and Its Clinical Significance in Patients with Oral Squamous Cell Carcinoma","volume":"75","author":"Singh","year":"2023","journal-title":"Indian J. Otolaryngol. Head Neck Surg."},{"key":"ref_23","doi-asserted-by":"crossref","first-page":"152213","DOI":"10.1016\/j.anndiagpath.2023.152213","article-title":"Prognostic value of CD44 expression in oral squamous cell carcinoma: A meta-analysis","volume":"67","author":"Mirhashemi","year":"2023","journal-title":"Ann. Diagn. Pathol."},{"key":"ref_24","doi-asserted-by":"crossref","first-page":"1650","DOI":"10.1007\/s12672-025-03436-9","article-title":"CD44 overexpression as a mediator of drug resistance in oral cancer: A meta-analysis unveiling molecular underpinnings and therapeutic implications","volume":"16","author":"Miao","year":"2025","journal-title":"Discov. Oncol."},{"key":"ref_25","doi-asserted-by":"crossref","unstructured":"Petrovi\u0107, A., Mojsilovi\u0107, S., Bugarski, D., Jaukovi\u0107, A., Pokimica, B., and Ili\u0107, M.P. (2025). Expression of Putative Cancer Stem Cell Markers in Oral Squamous Cell Carcinoma: Correlation with Clinicopathological Features. Int. J. Mol. Sci., 26.","DOI":"10.3390\/ijms262210939"},{"key":"ref_26","doi-asserted-by":"crossref","unstructured":"Melo-Alvim, C., Neves, M.E., Santos, J.L., Abrunhosa-Branquinho, A.N., Barroso, T., Costa, L., and Ribeiro, L. (2022). Radiotherapy, Chemotherapy and Immunotherapy-Current Practice and Future Perspectives for Recurrent\/Metastatic Oral Cavity Squamous Cell Carcinoma. Diagnostics, 13.","DOI":"10.3390\/diagnostics13010099"},{"key":"ref_27","doi-asserted-by":"crossref","first-page":"200","DOI":"10.1007\/s12070-019-01760-5","article-title":"Clinical Profile and Quality of Life Assessment of Oral Cancer Patients Following Nasolabial Flap Reconstruction Surgery","volume":"72","author":"Shetty","year":"2020","journal-title":"Indian J. Otolaryngol. Head Neck Surg."},{"key":"ref_28","doi-asserted-by":"crossref","unstructured":"Feller, G., Ramiah, D., Mahomed, F., Feller, L., and Khammissa, R.A.G. (2025). Radiotherapy and Its Consequences in Relation to Oral Squamous Cell Carcinoma\u2014A Narrative Review. Radiation, 5.","DOI":"10.3390\/radiation5030026"},{"key":"ref_29","doi-asserted-by":"crossref","first-page":"3288","DOI":"10.1111\/cas.14145","article-title":"Bone invasion-targeted chemotherapy with a novel anionic platinum complex (3Pt) for oral squamous cell carcinoma","volume":"110","author":"Kasahara","year":"2019","journal-title":"Cancer Sci."},{"key":"ref_30","doi-asserted-by":"crossref","first-page":"101","DOI":"10.1007\/s10565-025-10048-0","article-title":"Oral squamous cell carcinoma: Insights into cellular heterogeneity, drug resistance, and evolutionary trajectories","volume":"41","author":"Zhou","year":"2025","journal-title":"Cell Biol. Toxicol."},{"key":"ref_31","doi-asserted-by":"crossref","unstructured":"Kujan, O., van Schaijik, B., and Farah, C.S. (2020). Immune Checkpoint Inhibitors in Oral Cavity Squamous Cell Carcinoma and Oral Potentially Malignant Disorders: A Systematic Review. Cancers, 12.","DOI":"10.3390\/cancers12071937"},{"key":"ref_32","doi-asserted-by":"crossref","unstructured":"Situmorang, P.C., Ilyas, S., Nugraha, S.E., Syahputra, R.A., and Nik Abd Rahman, N.M.A. (2024). Prospects of compounds of herbal plants as anticancer agents: A comprehensive review from molecular pathways. Front. Pharmacol., 15.","DOI":"10.3389\/fphar.2024.1387866"},{"key":"ref_33","unstructured":"Hood Salleh, R.S.H., Jaenicke, C., Gruenwald, J., and Abidin, Z.Z. (2016). Health Beauty from the Rainforest Malaysian Traditions of Ramuan, Editions Didier Mille."},{"key":"ref_34","first-page":"4","article-title":"Cosmos caudatus: A Possible Drug Candidate for Oral Squamous Cell Carcinoma","volume":"17","author":"Alhakam","year":"2021","journal-title":"Curr. Bioact. Compd."},{"key":"ref_35","first-page":"14","article-title":"A Comprehensive Review on Cosmos caudatus (Ulam Raja): Pharmacology, Ethnopharmacology, and Phytochemistry","volume":"1","author":"Moshawih","year":"2017","journal-title":"Int. Res. J. Educ. Sci."},{"key":"ref_36","doi-asserted-by":"crossref","first-page":"285","DOI":"10.18585\/inabj.v16i3.3137","article-title":"Cosmos caudatus Leaf Extract Triggers Apoptosis of HSC-3 Cancer Cells by Decreasing Bcl-2 and Increasing Bax","volume":"16","author":"Sandra","year":"2024","journal-title":"Indones. Biomed. J."},{"key":"ref_37","doi-asserted-by":"crossref","first-page":"321","DOI":"10.5005\/jp-journals-10015-1651","article-title":"Tasty Herb that Heals: A Review of Cosmos caudatus (Ulam Raja) and its Potential Uses in Dentistry","volume":"10","author":"Uzbek","year":"2019","journal-title":"World J. Dent."},{"key":"ref_38","doi-asserted-by":"crossref","first-page":"83","DOI":"10.26656\/fr.2017.5(3).710","article-title":"Antimicrobial stability of Cosmos caudatus extract at varies pH and temperature, and compounds identification for application as food sanitiser","volume":"5","author":"Yusoff","year":"2021","journal-title":"Food Res."},{"key":"ref_39","doi-asserted-by":"crossref","unstructured":"Molina-Montes, E., Salamanca-Fern\u00e1ndez, E., Garcia-Villanova, B., and S\u00e1nchez, M.J. (2020). The Impact of Plant-Based Dietary Patterns on Cancer-Related Outcomes: A Rapid Review and Meta-Analysis. Nutrients, 12.","DOI":"10.3390\/nu12072010"},{"key":"ref_40","doi-asserted-by":"crossref","unstructured":"Menegassi, B., and Vinciguerra, M. (2025). Ultraprocessed Food and Risk of Cancer: Mechanistic Pathways and Public Health Implications. Cancers, 17.","DOI":"10.3390\/cancers17132064"},{"key":"ref_41","doi-asserted-by":"crossref","first-page":"e2023092","DOI":"10.4178\/epih.e2023092","article-title":"Cancer risk based on alcohol consumption levels: A comprehensive systematic review and meta-analysis","volume":"45","author":"Jun","year":"2023","journal-title":"Epidemiol. Health"},{"key":"ref_42","doi-asserted-by":"crossref","first-page":"243","DOI":"10.18585\/inabj.v10i3.441","article-title":"The Antioxidant and Cytotoxic Effects of Cosmos caudatus Ethanolic Extract on Cervical Cancer","volume":"10","author":"Nurhayati","year":"2018","journal-title":"Indones. Biomed. J."},{"key":"ref_43","first-page":"21","article-title":"Apoptotic Effect of Kenikir Leaves (Cosmos caudatus Kunth.) Methanolic Extract on Breast Cancer Cell Line","volume":"9","author":"Pebriana","year":"2008","journal-title":"Pharmaco"},{"key":"ref_44","doi-asserted-by":"crossref","first-page":"200","DOI":"10.22159\/ajpcr.2018.v11i1.21987","article-title":"Flavonoids from endophytic bacteria of Cosmos caudatus Kunth. Leaf as anticancer and antimicrobial","volume":"11","author":"Ramadhan","year":"2018","journal-title":"Asian J. Pharm. Clin. Res."},{"key":"ref_45","doi-asserted-by":"crossref","first-page":"78","DOI":"10.3892\/ol.2022.13198","article-title":"Quercetin induces tongue squamous cell carcinoma cell apoptosis via the JNK activation-regulated ERK\/GSK-3\u03b1\/\u03b2-mediated mitochondria-dependent apoptotic signaling pathway","volume":"23","author":"Huang","year":"2022","journal-title":"Oncol. Lett."},{"key":"ref_46","unstructured":"Fita, F.E., Listianingsih, D., Hapsari, Y.A., Pradana, R.G., Safitri, E.I., and Arifin, I. (2015). Efek Sitotoksik Kombinasi Ekstrak Metanol Daun Kenikir (Cosmos caudatus, Kunth) dan Doksorubisin Terhadap Sel Kanser Payudara T47D Secara In-Vitro dan In-Silico. Prosiding Seminar Nasional \u201cPeluang Herbal Sebagai Alternative Medicine\u201d. J. Ilmu Farm. Dan Farm. Klin., 51\u201356."},{"key":"ref_47","doi-asserted-by":"crossref","first-page":"2515","DOI":"10.13005\/bpj\/3274","article-title":"Polyphenols Target Apoptosis and Cell Cycle Regulation in Various Cancer Models: Emphasis on Flavonoid Subclasses","volume":"18","author":"Cheriyan","year":"2025","journal-title":"Biomed. Pharmacol. J."},{"key":"ref_48","doi-asserted-by":"crossref","first-page":"21695","DOI":"10.1038\/s41598-022-25744-8","article-title":"The mutational spectrum in whole exon of p53 in oral squamous cell carcinoma and its clinical implications","volume":"12","author":"Hyodo","year":"2022","journal-title":"Sci. Rep."},{"key":"ref_49","doi-asserted-by":"crossref","first-page":"81","DOI":"10.1007\/s12247-025-09989-0","article-title":"Unveiling the Pharmacological Mechanism of Cosmos caudatus Compounds as Lung Cancer Drug Candidates: Pharmacology Networking, Molecular Docking, and Experimental Validation","volume":"20","author":"Umar","year":"2025","journal-title":"J. Pharm. Innov."},{"key":"ref_50","first-page":"260","article-title":"Total Phenolic Content and Antioxidant Activity of Ulam Raja (Cosmos caudatus) and Quantification of its Selected Marker Compounds: Effect of Extraction","volume":"20","author":"Tan","year":"2016","journal-title":"Int. J. Food Prop."},{"key":"ref_51","doi-asserted-by":"crossref","first-page":"556","DOI":"10.1016\/j.foodchem.2014.12.013","article-title":"Interactions of polyphenols with carbohydrates, lipids and proteins","volume":"175","author":"Jakobek","year":"2015","journal-title":"Food Chem."},{"key":"ref_52","doi-asserted-by":"crossref","unstructured":"Wr\u00f3blewski, M., Wr\u00f3blewska, W., and Sobiesiak, M. (2024). The Role of Selected Elements in Oxidative Stress Protection: Key to Healthy Fertility and Reproduction. Int. J. Mol. Sci., 25.","DOI":"10.3390\/ijms25179409"},{"key":"ref_53","first-page":"275","article-title":"The positive impact of Vitamin C (Ascorbic Acid) utilisation in cancer treatment: A scoping review of published articles from the perspective of the in vitro studies","volume":"17","author":"Hamdi","year":"2021","journal-title":"Malays. J. Med. Health Sci."},{"key":"ref_54","doi-asserted-by":"crossref","unstructured":"You, A.J., Park, J., Shin, J.-M., and Kim, T.H. (2025). Oxidative Stress and Dietary Antioxidants in Head and Neck Cancer. Antioxidants, 14.","DOI":"10.3390\/antiox14050508"},{"key":"ref_55","doi-asserted-by":"crossref","unstructured":"Zhou, J., Chen, C., Chen, X., Fei, Y., Jiang, L., and Wang, G. (2020). Vitamin C Promotes Apoptosis and Cell Cycle Arrest in Oral Squamous Cell Carcinoma. Front. Oncol., 10.","DOI":"10.3389\/fonc.2020.00976"},{"key":"ref_56","doi-asserted-by":"crossref","first-page":"39","DOI":"10.51847\/y8iqIdTHhl","article-title":"Influence of Vitamins and Antioxidants in Oral Carcinogenesis\u2014A Review","volume":"14","author":"Daniela","year":"2023","journal-title":"Pharmacophore"},{"key":"ref_57","doi-asserted-by":"crossref","unstructured":"Andr\u00e9s, C.M., P\u00e9rez de la Lastra, J.M., Juan, C.A., Plou, F.J., and P\u00e9rez-Lebe\u00f1a, E. (2023). Polyphenols as Antioxidant\/Pro-Oxidant Compounds and Donors of Reducing Species: Relationship with Human Antioxidant Metabolism. Processes, 11.","DOI":"10.3390\/pr11092771"},{"key":"ref_58","doi-asserted-by":"crossref","first-page":"e1900400","DOI":"10.1002\/cbdv.201900400","article-title":"Recent Advances of Natural Polyphenols Activators for Keap1-Nrf2 Signaling Pathway","volume":"16","author":"Zhou","year":"2019","journal-title":"Chem. Biodivers."},{"key":"ref_59","doi-asserted-by":"crossref","first-page":"154","DOI":"10.1016\/j.cbi.2011.12.005","article-title":"Quercetin modulates Nrf2 and glutathione-related defenses in HepG2 cells: Involvement of p38","volume":"195","author":"Bravo","year":"2012","journal-title":"Chem.-Biol. Interact."},{"key":"ref_60","doi-asserted-by":"crossref","unstructured":"Qi, W., Qi, W., Xiong, D., and Long, M. (2022). Quercetin: Its Antioxidant Mechanism, Antibacterial Properties and Potential Application in Prevention and Control of Toxipathy. Molecules, 27.","DOI":"10.3390\/molecules27196545"},{"key":"ref_61","doi-asserted-by":"crossref","unstructured":"Xu, D., Hu, M.J., Wang, Y.Q., and Cui, Y.L. (2019). Antioxidant Activities of Quercetin and Its Complexes for Medicinal Application. Molecules, 24.","DOI":"10.3390\/molecules24061123"},{"key":"ref_62","doi-asserted-by":"crossref","first-page":"1000","DOI":"10.4103\/1735-1995.172796","article-title":"Potential medicinal benefits of Cosmos caudatus (Ulam Raja): A scoping review","volume":"20","author":"Cheng","year":"2015","journal-title":"J. Res. Med. Sci."},{"key":"ref_63","doi-asserted-by":"crossref","unstructured":"Anttila, J.V., Shubin, M., Cairns, J., Borse, F., Guo, Q., Mononen, T., V\u00e1zquez-Garc\u00eda, I., Pulkkinen, O., and Mustonen, V. (2019). Contrasting the impact of cytotoxic and cytostatic drug therapies on tumour progression. PLoS Comput. Biol., 15.","DOI":"10.1371\/journal.pcbi.1007493"},{"key":"ref_64","doi-asserted-by":"crossref","first-page":"115646","DOI":"10.1016\/j.taap.2021.115646","article-title":"Cisplatin induces autophagy-associated apoptosis in human oral squamous cell carcinoma (OSCC) mediated in part through reactive oxygen species","volume":"427","author":"Magnano","year":"2021","journal-title":"Toxicol. Appl. Pharmacol."},{"key":"ref_65","first-page":"6038","article-title":"Oral squamous cell carcinoma cancer stem cells have different drug sensitive to pharmacological NF\u03baB and histone deacetylation inhibition","volume":"13","author":"Silva","year":"2023","journal-title":"Am. J. Cancer Res."},{"key":"ref_66","doi-asserted-by":"crossref","unstructured":"Khoo, X.H., Paterson, I.C., Goh, B.H., and Lee, W.L. (2019). Cisplatin-Resistance in Oral Squamous Cell Carcinoma: Regulation by Tumor Cell-Derived Extracellular Vesicles. Cancers, 11.","DOI":"10.3390\/cancers11081166"},{"key":"ref_67","doi-asserted-by":"crossref","first-page":"107238","DOI":"10.1016\/j.vascn.2022.107238","article-title":"Non-uniformity in in vitro drug-induced cytotoxicity as evidenced by differences in IC50 values\u2014Implications and way forward","volume":"119","author":"Barghavi","year":"2023","journal-title":"J. Pharmacol. Toxicol. Methods"},{"key":"ref_68","doi-asserted-by":"crossref","first-page":"92","DOI":"10.1038\/s41392-023-01347-1","article-title":"Targeting p53 pathways: Mechanisms, structures and advances in therapy","volume":"8","author":"Wang","year":"2023","journal-title":"Signal Transduct. Target. Ther."},{"key":"ref_69","doi-asserted-by":"crossref","first-page":"7","DOI":"10.3892\/ijmm.2024.5448","article-title":"TP53 mutations in cancer: Molecular features and therapeutic opportunities (Review)","volume":"55","author":"Tornesello","year":"2025","journal-title":"Int. J. Mol. Med."},{"key":"ref_70","doi-asserted-by":"crossref","unstructured":"Shi, T., Polderman, P.E., Burgering, B.M.T., and Dansen, T.B. (2020). DNA damage and oxidizing conditions activate p53 through differential upstream signaling pathways. bioRxiv, bioRxiv:2020.09.13.295220.","DOI":"10.1101\/2020.09.13.295220"},{"key":"ref_71","doi-asserted-by":"crossref","first-page":"1942","DOI":"10.1038\/s41598-023-29060-7","article-title":"Fetal bovine serum, an important factor affecting the reproducibility of cell experiments","volume":"13","author":"Liu","year":"2023","journal-title":"Sci. Rep."},{"key":"ref_72","doi-asserted-by":"crossref","unstructured":"Mun, S.E., Sim, B.W., Yoon, S.B., Jeong, P.S., Yang, H.J., Choi, S.A., Park, Y.H., Kim, Y.H., Kang, P., and Jeong, K.J. (2017). Dual effect of fetal bovine serum on early development depends on stage-specific reactive oxygen species demands in pigs. PLoS ONE, 12.","DOI":"10.1371\/journal.pone.0175427"},{"key":"ref_73","first-page":"5013409","article-title":"FBS or BSA Inhibits EGCG Induced Cell Death through Covalent Binding and the Reduction of Intracellular ROS Production","volume":"2016","author":"Zhang","year":"2016","journal-title":"BioMed. Res. Int."},{"key":"ref_74","doi-asserted-by":"crossref","first-page":"1529","DOI":"10.1016\/j.freeradbiomed.2008.01.011","article-title":"ROS and p53: A versatile partnership","volume":"44","author":"Liu","year":"2008","journal-title":"Free Radic. Biol. Med."},{"key":"ref_75","doi-asserted-by":"crossref","first-page":"174147","DOI":"10.1016\/j.ejphar.2021.174147","article-title":"The role of CD44 in cancer chemoresistance: A concise review","volume":"903","author":"Yaghobi","year":"2021","journal-title":"Eur. J. Pharmacol."},{"key":"ref_76","doi-asserted-by":"crossref","first-page":"14","DOI":"10.1016\/j.jfda.2019.11.001","article-title":"Recent advances in cancer chemoprevention with phytochemicals","volume":"28","author":"Koh","year":"2020","journal-title":"J. Food Drug Anal."},{"key":"ref_77","doi-asserted-by":"crossref","first-page":"64","DOI":"10.1186\/s13045-018-0605-5","article-title":"The biology and role of CD44 in cancer progression: Therapeutic implications","volume":"11","author":"Chen","year":"2018","journal-title":"J. Hematol. Oncol."},{"key":"ref_78","doi-asserted-by":"crossref","first-page":"387","DOI":"10.3892\/ijo.2016.3821","article-title":"Induced overexpression of CD44 associated with resistance to apoptosis on DNA damage response in human head and neck squamous cell carcinoma cells","volume":"50","author":"Ohkoshi","year":"2017","journal-title":"Int. J. Oncol."},{"key":"ref_79","doi-asserted-by":"crossref","unstructured":"Wu, Z., Lu, J., Loo, A., Ho, N., Nguyen, D., Cheng, P.Y., Mohammed, A.I., and Cirillo, N. (2024). Role of CD44 in Chemotherapy Treatment Outcome: A Scoping Review of Clinical Studies. Int. J. Mol. Sci., 25.","DOI":"10.3390\/ijms25063141"},{"key":"ref_80","doi-asserted-by":"crossref","first-page":"101644","DOI":"10.1016\/j.tranon.2023.101644","article-title":"CD44 occurring alternative splicing promotes cisplatin resistance and evokes tumor immune response in oral squamous cell carcinoma cells","volume":"31","author":"Qiao","year":"2023","journal-title":"Transl. Oncol."},{"key":"ref_81","doi-asserted-by":"crossref","first-page":"162","DOI":"10.3892\/or.2023.8599","article-title":"Mutant p53 in head and neck squamous cell carcinoma: Molecular mechanism of gain-of-function and targeting therapy (Review)","volume":"50","author":"Li","year":"2023","journal-title":"Oncol. Rep."},{"key":"ref_82","doi-asserted-by":"crossref","first-page":"337","DOI":"10.5125\/jkaoms.2016.42.6.337","article-title":"The influence of p53 mutation status on the anti-cancer effect of cisplatin in oral squamous cell carcinoma cell lines","volume":"42","author":"Jo","year":"2016","journal-title":"J. Korean Assoc. Oral. Maxillofac. Surg."},{"key":"ref_83","doi-asserted-by":"crossref","first-page":"104660","DOI":"10.1016\/j.yexmp.2021.104660","article-title":"The cell theory and cellular pathology: Discovery, refinements and applications fundamental to advances in biology and medicine","volume":"121","author":"Buja","year":"2021","journal-title":"Exp. Mol. Pathol."},{"key":"ref_84","first-page":"9990489","article-title":"High CD44 Immunoexpression Correlates with Poor Overall Survival: Assessing the Role of Cancer Stem Cell Markers in Oral Squamous Cell Carcinoma Patients from the High-Risk Population of Pakistan","volume":"2022","author":"Adnan","year":"2022","journal-title":"Int. J. Surg. Oncol."},{"key":"ref_85","first-page":"255","article-title":"A Immunohistochemical Expression of p53 in Oral Squamous Cell Carcinoma, Oral Epithelial Precursor Lesions, and Normal Oral Mucosa","volume":"29","author":"Khan","year":"2022","journal-title":"J. Med. Sci."},{"key":"ref_86","doi-asserted-by":"crossref","first-page":"344","DOI":"10.1080\/10942912.2022.2158862","article-title":"A review on Cosmos caudatus as A potential medicinal plant based on pharmacognosy, phytochemistry, and pharmacological activities","volume":"26","author":"Ahda","year":"2023","journal-title":"Int. J. Food Prop."},{"key":"ref_87","doi-asserted-by":"crossref","unstructured":"Hashim, G.M., Shahgolzari, M., Hefferon, K., Yavari, A., and Venkataraman, S. (2025). Plant-Derived Anti-Cancer Therapeutics and Biopharmaceuticals. Bioengineering, 12.","DOI":"10.20944\/preprints202411.1065.v1"},{"key":"ref_88","doi-asserted-by":"crossref","first-page":"1061","DOI":"10.31557\/apjcb.2025.10.4.1061-1074","article-title":"Chemoprotective Horizons: Bioactive Molecules as Therapeutic Shields Against Cytotoxicity","volume":"10","author":"Martin","year":"2025","journal-title":"Asian Pac. J. Cancer Biol."},{"key":"ref_89","doi-asserted-by":"crossref","first-page":"1099","DOI":"10.1158\/2159-8290.CD-24-1638","article-title":"Mutant p53 Gain of Function: Why Many See It, Why Some Do Not","volume":"15","author":"Lozano","year":"2025","journal-title":"Cancer Discov."},{"key":"ref_90","doi-asserted-by":"crossref","first-page":"974","DOI":"10.1038\/s41419-022-05408-1","article-title":"Mutant p53 in cancer: From molecular mechanism to therapeutic modulation","volume":"13","author":"Chen","year":"2022","journal-title":"Cell Death Dis."},{"key":"ref_91","doi-asserted-by":"crossref","unstructured":"Wang, J., Liu, W., Zhang, L., and Zhang, J. (2023). Targeting mutant p53 stabilization for cancer therapy. Front. Pharmacol., 14.","DOI":"10.3389\/fphar.2023.1215995"},{"key":"ref_92","doi-asserted-by":"crossref","first-page":"10732748241302902","DOI":"10.1177\/10732748241302902","article-title":"Phytochemicals in Cancer Chemoprevention: Preclinical and Clinical Studies","volume":"31","author":"Lekhak","year":"2024","journal-title":"Cancer Control"},{"key":"ref_93","doi-asserted-by":"crossref","unstructured":"Rao, M.J., Duan, M., Zhou, C., Jiao, J., Cheng, P., Yang, L., Wei, W., Shen, Q., Ji, P., and Yang, Y. (2025). Antioxidant Defense System in Plants: Reactive Oxygen Species Production, Signaling, and Scavenging During Abiotic Stress-Induced Oxidative Damage. Horticulturae, 11.","DOI":"10.3390\/horticulturae11050477"},{"key":"ref_94","doi-asserted-by":"crossref","unstructured":"Ghasemi, M., Turnbull, T., Sebastian, S., and Kempson, I. (2021). The MTT Assay: Utility, Limitations, Pitfalls, and Interpretation in Bulk and Single-Cell Analysis. Int. J. Mol. Sci., 22.","DOI":"10.3390\/ijms222312827"},{"key":"ref_95","doi-asserted-by":"crossref","first-page":"10","DOI":"10.1016\/j.gde.2020.10.007","article-title":"Allele-specific expression: Applications in cancer and technical considerations","volume":"66","author":"Mohammadi","year":"2021","journal-title":"Curr. Opin. Genet. Dev."},{"key":"ref_96","doi-asserted-by":"crossref","first-page":"7","DOI":"10.1007\/978-1-0716-1217-0_2","article-title":"Detection of Post-translationally Modified p53 by Western Blotting","volume":"2267","author":"Barber","year":"2021","journal-title":"Methods Mol. Biol."},{"key":"ref_97","doi-asserted-by":"crossref","first-page":"1407","DOI":"10.1177\/00220345940730080301","article-title":"Regulation of PG synthase by EGF and PDGF in human oral, breast, stomach, and fibrosarcoma cancer cell lines","volume":"73","author":"Yang","year":"1994","journal-title":"J. Dent. Res."},{"key":"ref_98","doi-asserted-by":"crossref","unstructured":"Camacho-Alonso, F., G\u00f3mez-Albentosa, T., O\u00f1ate-S\u00e1nchez, R.E., Tudela-Mulero, M.R., S\u00e1nchez-Siles, M., G\u00f3mez-Garc\u00eda, F.J., and Guerrero-S\u00e1nchez, Y. (2020). In Vitro Study of Synergic Effect of Cisplatin and Low Molecular Weight Heparin on Oral Squamous Cell Carcinoma. Front. Oncol., 10.","DOI":"10.3389\/fonc.2020.549412"},{"key":"ref_99","doi-asserted-by":"crossref","first-page":"7","DOI":"10.1007\/978-1-61779-108-6_2","article-title":"Cell viability analysis using trypan blue: Manual and automated methods","volume":"740","author":"Louis","year":"2011","journal-title":"Methods Mol. Biol."},{"key":"ref_100","unstructured":"(2009). Biological Evaluation of Medical Devices\u2014Part 5: Tests for In Vitro Cytotoxicity (Standard No. ISO 10993-5:2009)."},{"key":"ref_101","doi-asserted-by":"crossref","first-page":"739","DOI":"10.1530\/ERC-19-0107","article-title":"Potentiated anti-tumor effects of BETi by MEKi in anaplastic thyroid cancer","volume":"26","author":"Zhu","year":"2019","journal-title":"Endocr. Relat. Cancer"},{"key":"ref_102","doi-asserted-by":"crossref","first-page":"2470","DOI":"10.7150\/ijms.112735","article-title":"Exploring Renin-angiotensin System Genes as Novel Prognostic Biomarkers for Oral Squamous Cell Carcinoma","volume":"22","author":"Wu","year":"2025","journal-title":"Int. J. Med. Sci."}],"container-title":["International Journal of Molecular Sciences"],"original-title":[],"language":"en","link":[{"URL":"https:\/\/www.mdpi.com\/1422-0067\/27\/14\/6361\/pdf","content-type":"unspecified","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2026,7,21]],"date-time":"2026-07-21T04:22:13Z","timestamp":1784607733000},"score":1,"resource":{"primary":{"URL":"https:\/\/www.mdpi.com\/1422-0067\/27\/14\/6361"}},"subtitle":[],"short-title":[],"issued":{"date-parts":[[2026,7,17]]},"references-count":102,"journal-issue":{"issue":"14","published-online":{"date-parts":[[2026,7]]}},"alternative-id":["ijms27146361"],"URL":"https:\/\/doi.org\/10.3390\/ijms27146361","relation":{},"ISSN":["1422-0067"],"issn-type":[{"value":"1422-0067","type":"electronic"}],"subject":[],"published":{"date-parts":[[2026,7,17]]}}}