{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,8,18]],"date-time":"2026-08-18T13:30:05Z","timestamp":1787059805180,"version":"build-2736575974"},"reference-count":45,"publisher":"MDPI AG","issue":"16","license":[{"start":{"date-parts":[[2026,8,18]],"date-time":"2026-08-18T00:00:00Z","timestamp":1787011200000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"funder":[{"name":"Faculty of Allied Health Sciences, Naresuan University, Thailand","award":["AH-64-01-003 (R2564E088)"],"award-info":[{"award-number":["AH-64-01-003 (R2564E088)"]}]},{"award":["AH-64-01-003 (R2564E088)"],"award-info":[{"award-number":["AH-64-01-003 (R2564E088)"]}],"id":[{"id":"https:\/\/ror.org\/03e2qe334","id-type":"ROR","asserted-by":"publisher"}]}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":["Cells"],"abstract":"<jats:p>Radiosensitizers are being investigated to improve the therapeutic efficacy of radiotherapy by enhancing tumor cell sensitivity while minimizing damage to normal tissues. Dihydroquinine (DHQ), a naturally occurring Cinchona alkaloid with diverse biological activities, has not previously been evaluated for radiosensitizing potential. In this study, human cervical cancer (HeLa) cells were pretreated with an IC20 concentration of DHQ and exposed to 6 MV X-ray irradiation. Clonogenic survival was assessed after irradiation at 2, 4, and 6 Gy, while intracellular ROS, \u03b3-H2AX immunofluorescence, and apoptosis were evaluated following DHQ pretreatment and 2 Gy irradiation. DHQ pretreatment reduced clonogenic survival, yielding sensitizer enhancement ratio values of 1.37 and 1.55 at surviving fractions of 0.20 and 0.37, respectively, indicating modest-to-moderate enhancement of radiosensitivity. DHQ was also associated with increased ROS production, elevated \u03b3-H2AX positivity, and enhanced apoptosis compared with irradiation alone. These findings suggest that DHQ enhances the radiation response in HeLa cells and is associated with increased radiation-induced cellular responses. Although the radiosensitizing effect was modest, the consistent findings across multiple biological endpoints support further investigation of DHQ as a potential adjunct to radiotherapy. Further studies are warranted to validate these findings in more clinically relevant preclinical models.<\/jats:p>","DOI":"10.3390\/cells15161484","type":"journal-article","created":{"date-parts":[[2026,8,18]],"date-time":"2026-08-18T13:11:57Z","timestamp":1787058717000},"page":"1484","update-policy":"https:\/\/doi.org\/10.3390\/mdpi_crossmark_policy","source":"Crossref","is-referenced-by-count":0,"title":["Dihydroquinine Enhances Radiosensitivity in Cervical Cancer Cells Accompanied by Radiation-Induced Cellular Responses"],"prefix":"10.3390","volume":"15","author":[{"ORCID":"https:\/\/orcid.org\/0000-0003-1494-1680","authenticated-orcid":false,"given":"Ausanai","family":"Prapan","sequence":"first","affiliation":[{"name":"Department of Radiological Technology, Faculty of Allied Health Sciences, Naresuan University, Mueang District, Phitsanulok 65000, Thailand"},{"name":"Institute of Transfusion Medicine, Charit\u00e9-Universit\u00e4tsmedizin Berlin, 10117 Berlin, Germany"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Pimvaree","family":"Aissara","sequence":"additional","affiliation":[{"name":"Department of Radiological Technology, Faculty of Allied Health Sciences, Naresuan University, Mueang District, Phitsanulok 65000, Thailand"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0009-0008-9469-7633","authenticated-orcid":false,"given":"Peerawit","family":"Soonthornchookiat","sequence":"additional","affiliation":[{"name":"Department of Radiological Technology, Faculty of Allied Health Sciences, Naresuan University, Mueang District, Phitsanulok 65000, Thailand"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0009-0005-8161-9730","authenticated-orcid":false,"given":"Chanyatip","family":"Suwannasing","sequence":"additional","affiliation":[{"name":"Department of Radiological Technology, Faculty of Allied Health Sciences, Naresuan University, Mueang District, Phitsanulok 65000, Thailand"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-0854-3475","authenticated-orcid":false,"given":"Jirapas","family":"Jongjitwimol","sequence":"additional","affiliation":[{"name":"Department of Medical Technology, Faculty of Allied Health Sciences, Naresuan University, Mueang District, Phitsanulok 65000, Thailand"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Chatrawut","family":"Pattaweerakul","sequence":"additional","affiliation":[{"name":"Department of Radiology, Faculty of Medicine, Naresuan University, Mueang District, Phitsanulok 65000, Thailand"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-2445-8185","authenticated-orcid":false,"given":"Yu","family":"Xiong","sequence":"additional","affiliation":[{"name":"Institute of Transfusion Medicine, Charit\u00e9-Universit\u00e4tsmedizin Berlin, 10117 Berlin, Germany"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Saranya","family":"Chaiwaree","sequence":"additional","affiliation":[{"name":"Department of Pharmaceutical Technology and Biotechnology, Faculty of Pharmacy, Payap University, Chiang Mai 50210, Thailand"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-2573-2289","authenticated-orcid":false,"given":"Hans","family":"B\u00e4umler","sequence":"additional","affiliation":[{"name":"Institute of Transfusion Medicine, Charit\u00e9-Universit\u00e4tsmedizin Berlin, 10117 Berlin, Germany"},{"name":"Department of Pharmaceutical Technology and Biotechnology, Faculty of Pharmacy, Payap University, Chiang Mai 50210, Thailand"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"1968","published-online":{"date-parts":[[2026,8,18]]},"reference":[{"key":"ref_1","doi-asserted-by":"crossref","unstructured":"Jouya, S., Shahabinia, Z., Mazidimoradi, A., Allahqoli, L., Salehiniya, H., and Lee, D.-Y. (2026). Cervical Cancer Epidemiology: Global Incidence, Mortality, Survival, Risk Factors, and Equity in HPV Screening and Vaccination. J. Clin. Med., 15.","DOI":"10.3390\/jcm15031079"},{"key":"ref_2","doi-asserted-by":"crossref","unstructured":"Zhou, L., Li, Y., Wang, H., Qin, R., Han, Z., and Li, R. (2025). Global Cervical Cancer Elimination: Quantifying the Status, Progress, and Gaps. BMC Med., 23.","DOI":"10.1186\/s12916-025-03897-3"},{"key":"ref_3","doi-asserted-by":"crossref","first-page":"64","DOI":"10.1007\/s44178-025-00200-5","article-title":"Review of Radiotherapy for Cervical Cancer","volume":"4","author":"Zhang","year":"2025","journal-title":"Holist. Integr. Oncol."},{"key":"ref_4","doi-asserted-by":"crossref","first-page":"436","DOI":"10.1136\/ijgc-2021-003001","article-title":"Global Challenges of Radiotherapy for the Treatment of Locally Advanced Cervical Cancer","volume":"32","author":"Mayadev","year":"2022","journal-title":"Int. J. Gynecol. Cancer"},{"key":"ref_5","doi-asserted-by":"crossref","unstructured":"Zhou, Y., Rassy, E., Coutte, A., Achkar, S., Espenel, S., Genestie, C., Pautier, P., Morice, P., Gouy, S., and Chargari, C. (2022). Current Standards in the Management of Early and Locally Advanced Cervical Cancer: Update on the Benefit of Neoadjuvant\/Adjuvant Strategies. Cancers, 14.","DOI":"10.3390\/cancers14102449"},{"key":"ref_6","doi-asserted-by":"crossref","first-page":"1083","DOI":"10.2147\/IJN.S290438","article-title":"Application of Radiosensitizers in Cancer Radiotherapy","volume":"16","author":"Gong","year":"2021","journal-title":"Int. J. Nanomed."},{"key":"ref_7","first-page":"100419","article-title":"Advancing Cancer Radiotherapy: Harnessing Radiosensitizers and Nanotechnology for Enhanced Tumor Control","volume":"10","author":"Shiridokht","year":"2025","journal-title":"Int. J. Pharm. X"},{"key":"ref_8","doi-asserted-by":"crossref","unstructured":"Ronsini, C., Solazzo, M.C., Braca, E., Andreoli, G., Vastarella, M.G., Cianci, S., Capozzi, V.A., Torella, M., Cobellis, L., and De Franciscis, P. (2024). Locally Advanced Cervical Cancer: Neoadjuvant Treatment versus Standard Radio-Chemotherapy\u2014An Updated Meta-Analysis. Cancers, 16.","DOI":"10.3390\/cancers16142542"},{"key":"ref_9","doi-asserted-by":"crossref","unstructured":"Massobrio, R., Bianco, L., Campigotto, B., Attianese, D., Maisto, E., Pascotto, M., Ruo Redda, M.G., and Ferrero, A. (2024). New Frontiers in Locally Advanced Cervical Cancer Treatment. J. Clin. Med., 13.","DOI":"10.3390\/jcm13154458"},{"key":"ref_10","doi-asserted-by":"crossref","first-page":"106939","DOI":"10.1016\/j.ejps.2024.106939","article-title":"Advances in Understanding Cisplatin-Induced Toxicity: Molecular Mechanisms and Protective Strategies","volume":"203","author":"Elmorsy","year":"2024","journal-title":"Eur. J. Pharm. Sci."},{"key":"ref_11","doi-asserted-by":"crossref","unstructured":"Mavragani, I.V., Nikitaki, Z., Souli, M.P., Aziz, A., Nowsheen, S., Aziz, K., Rogakou, E., and Georgakilas, A.G. (2017). Complex DNA Damage: A Route to Radiation-Induced Genomic Instability and Carcinogenesis. Cancers, 9.","DOI":"10.3390\/cancers9070091"},{"key":"ref_12","doi-asserted-by":"crossref","first-page":"119","DOI":"10.31482\/mmsl.2018.016","article-title":"Dose-Rate as a Critical Aspect of Cellular Response to Gamma-Radiation","volume":"87","year":"2018","journal-title":"Mil. Med. Sci. Lett."},{"key":"ref_13","doi-asserted-by":"crossref","unstructured":"Carlos-Reyes, A., Mu\u00f1iz-Lino, M.A., Romero-Garcia, S., L\u00f3pez-Camarillo, C., and Hern\u00e1ndez-de la Cruz, O.N. (2021). Biological Adaptations of Tumor Cells to Radiation Therapy. Front. Oncol., 11.","DOI":"10.3389\/fonc.2021.718636"},{"key":"ref_14","doi-asserted-by":"crossref","first-page":"113610","DOI":"10.1016\/j.biopha.2022.113610","article-title":"Natural Products as Chemo-Radiation Therapy Sensitizers in Cancers","volume":"154","author":"Nisar","year":"2022","journal-title":"Biomed. Pharmacother."},{"key":"ref_15","doi-asserted-by":"crossref","first-page":"11","DOI":"10.1055\/a-2654-6072","article-title":"Phytochemicals as Radioprotective and Radiosensitizing Agents in Cancer Radiotherapy: Advances, Challenges, and Future Perspectives","volume":"92","author":"Dweh","year":"2026","journal-title":"Planta Medica"},{"key":"ref_16","doi-asserted-by":"crossref","first-page":"117","DOI":"10.1016\/j.chroma.2018.04.038","article-title":"Quantitative Determination of Major Alkaloids in Cinchona Bark by Supercritical Fluid Chromatography","volume":"1554","author":"Murauer","year":"2018","journal-title":"J. Chromatogr. A"},{"key":"ref_17","doi-asserted-by":"crossref","first-page":"e70560","DOI":"10.1002\/jbt.70560","article-title":"Exploring the Anticancer Properties of Cinchonine: A Comprehensive Review of Cellular and Molecular Mechanisms with Botanical Source and Pharmacokinetics Property","volume":"39","author":"Rakib","year":"2025","journal-title":"J. Biochem. Mol. Toxicol."},{"key":"ref_18","doi-asserted-by":"crossref","unstructured":"Weawsiangsang, S., Rattanachak, N., Jongjitvimol, T., Jaifoo, T., Charoensit, P., Viyoch, J., Ross, S., Ross, G.M., Baldock, R.A., and Jongjitwimol, J. (2023). Hydroquinine Inhibits the Growth of Multidrug-Resistant Pseudomonas Aeruginosa via the Suppression of the Arginine Deiminase Pathway Genes. Int. J. Mol. Sci., 24.","DOI":"10.3390\/ijms241813914"},{"key":"ref_19","doi-asserted-by":"crossref","unstructured":"Rattanachak, N., Weawsiangsang, S., Jongjitvimol, T., Baldock, R.A., and Jongjitwimol, J. (2022). Hydroquinine Possesses Antibacterial Activity, and at Half the MIC, Induces the Overexpression of RND-Type Efflux Pumps Using Multiplex Digital PCR in Pseudomonas Aeruginosa. Trop. Med. Infect. Dis., 7.","DOI":"10.3390\/tropicalmed7080156"},{"key":"ref_20","doi-asserted-by":"crossref","unstructured":"Rattanachak, N., Weawsiangsang, S., Daowtak, K., Thongsri, Y., Ross, S., Ross, G., Nilsri, N., Baldock, R.A., Pongcharoen, S., and Jongjitvimol, T. (2022). High-Throughput Transcriptomic Profiling Reveals the Inhibitory Effect of Hydroquinine on Virulence Factors in Pseudomonas Aeruginosa. Antibiotics, 11.","DOI":"10.3390\/antibiotics11101436"},{"key":"ref_21","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_22","doi-asserted-by":"crossref","first-page":"1501","DOI":"10.3892\/ijo.2013.1857","article-title":"Cell Survival and Radiosensitisation: Modulation of the Linear and Quadratic Parameters of the LQ Model","volume":"42","author":"Franken","year":"2013","journal-title":"Int. J. Oncol."},{"key":"ref_23","doi-asserted-by":"crossref","first-page":"229","DOI":"10.1093\/jrr\/rru085","article-title":"Radiosensitizing Effect of Carboplatin and Paclitaxel to Carbon-Ion Beam Irradiation in the Non-Small-Cell Lung Cancer Cell Line H460","volume":"56","author":"Kubo","year":"2015","journal-title":"J. Radiat. Res."},{"key":"ref_24","doi-asserted-by":"crossref","first-page":"628","DOI":"10.1038\/bjc.2011.240","article-title":"Guidelines for Preclinical and Early Phase Clinical Assessment of Novel Radiosensitisers","volume":"105","author":"Harrington","year":"2011","journal-title":"Br. J. Cancer"},{"key":"ref_25","doi-asserted-by":"crossref","unstructured":"Matsui, T., Nuryadi, E., Komatsu, S., Hirota, Y., Shibata, A., Oike, T., and Nakano, T. (2019). Robustness of Clonogenic Assays as a Biomarker for Cancer Cell Radiosensitivity. Int. J. Mol. Sci., 20.","DOI":"10.3390\/ijms20174148"},{"key":"ref_26","doi-asserted-by":"crossref","unstructured":"Oike, T., Hirota, Y., Darwis, N.D.M., Shibata, A., and Ohno, T. (2020). Comparison of Clonogenic Survival Data Obtained by Pre-and Post-Irradiation Methods. J. Pers. Med., 10.","DOI":"10.3390\/jpm10040171"},{"key":"ref_27","first-page":"2768","article-title":"Analysis of Oxidative Stress Markers in Plasma Derived from Individuals Exposed to Ionizing Radiation","volume":"15","author":"Nishiyama","year":"2019","journal-title":"Biomed. J. Sci. Tech. Res."},{"key":"ref_28","doi-asserted-by":"crossref","first-page":"e13409","DOI":"10.1111\/imr.13409","article-title":"A Comprehensive Review of Sensors of Radiation-Induced Damage, Radiation-Induced Proximal Events, and Cell Death","volume":"329","author":"Saini","year":"2025","journal-title":"Immunol. Rev."},{"key":"ref_29","doi-asserted-by":"crossref","unstructured":"Fiorica, F., Tebano, U., Napoli, G., Franceschetto, A., Muraro, M., Giorgi, C., and Pinton, P. (2025). Metabolic-Modulating Effects of Radiation: Undetectable Yet Deadly\u2014A Review on Radiotherapy. Cancers, 17.","DOI":"10.3390\/cancers17010054"},{"key":"ref_30","doi-asserted-by":"crossref","unstructured":"Nigam, M., Punia, B., Dimri, D.B., Mishra, A.P., Radu, A.F., and Bungau, G. (2025). Reactive Oxygen Species: A Double-Edged Sword in the Modulation of Cancer Signaling Pathway Dynamics. Cells, 14.","DOI":"10.3390\/cells14151207"},{"key":"ref_31","doi-asserted-by":"crossref","unstructured":"Nenoi, M. (2012). Measurement of H2AX Phosphorylation as a Marker of Ionizing Radiation Induced Cell Damage. Current Topics in Ionizing Radiation Research, InTech\/IntechOpen.","DOI":"10.5772\/2027"},{"key":"ref_32","doi-asserted-by":"crossref","first-page":"14360","DOI":"10.1038\/s41598-022-17830-8","article-title":"Computational Modelling of \u03b3-H2AX Foci Formation in Human Cells Induced by Alpha Particle Exposure","volume":"12","author":"Lee","year":"2022","journal-title":"Sci. Rep."},{"key":"ref_33","first-page":"e1957","article-title":"Quantification of \u0393H2AX Foci in Response to Ionising Radiation","volume":"38","author":"Mah","year":"2010","journal-title":"J. Vis. Exp."},{"key":"ref_34","doi-asserted-by":"crossref","unstructured":"Valente, D., Gentileschi, M.P., Guerrisi, A., Bruzzaniti, V., Morrone, A., Soddu, S., and Verdina, A. (2022). Factors to Consider for the Correct Use of \u0393H2AX in the Evaluation of DNA Double-Strand Breaks Damage Caused by Ionizing Radiation. Cancers, 14.","DOI":"10.3390\/cancers14246204"},{"key":"ref_35","first-page":"305","article-title":"Gamma-H2AX\u2014A Novel Biomarker for DNA Double-Strand Breaks","volume":"22","author":"Kuo","year":"2008","journal-title":"In Vivo"},{"key":"ref_36","doi-asserted-by":"crossref","first-page":"317","DOI":"10.1093\/jrr\/rrac096","article-title":"Optimal Timing of a \u03b3 H2AX Analysis to Predict Cellular Lethal Damage in Cultured Tumor Cell Lines after Exposure to Diagnostic and Therapeutic Radiation Doses","volume":"64","author":"Takano","year":"2023","journal-title":"J. Radiat. Res."},{"key":"ref_37","doi-asserted-by":"crossref","unstructured":"Zhao, Y., Ye, X., Xiong, Z., Ihsan, A., Ares, I., Mart\u00ednez, M., Lopez-Torres, B., Mart\u00ednez-Larra\u00f1aga, M.R., Anad\u00f3n, A., and Wang, X. (2023). Cancer Metabolism: The Role of ROS in DNA Damage and Induction of Apoptosis in Cancer Cells. Metabolites, 13.","DOI":"10.3390\/metabo13070796"},{"key":"ref_38","doi-asserted-by":"crossref","first-page":"957","DOI":"10.1038\/nrc2523","article-title":"\u0393H2AX and Cancer","volume":"8","author":"Bonner","year":"2008","journal-title":"Nat. Rev. Cancer"},{"key":"ref_39","doi-asserted-by":"crossref","first-page":"843","DOI":"10.1634\/theoncologist.2012-0455","article-title":"Comparison of Carboplatin- and Cisplatin-Based Concurrent Chemoradiotherapy in Locally Advanced Cervical Cancer Patients with Morbidity Risks","volume":"18","author":"Nam","year":"2013","journal-title":"Oncologist"},{"key":"ref_40","doi-asserted-by":"crossref","unstructured":"Tharavichitkul, E., Lorvidhaya, V., Kamnerdsupaphon, P., Sukthomya, V., Chakrabandhu, S., Klunklin, P., Onchan, W., Supawongwattana, B., Pukanhaphan, N., and Galalae, R. (2016). Combined Chemoradiation of Cisplatin versus Carboplatin in Cervical Carcinoma: A Single Institution Experience from Thailand. BMC Cancer, 16.","DOI":"10.1186\/s12885-016-2558-9"},{"key":"ref_41","doi-asserted-by":"crossref","first-page":"3815","DOI":"10.1038\/s41598-020-60765-1","article-title":"Modification of Radiosensitivity by Curcumin in Human Pancreatic Cancer Cell Lines","volume":"10","author":"Schwarz","year":"2020","journal-title":"Sci. Rep."},{"key":"ref_42","doi-asserted-by":"crossref","first-page":"101","DOI":"10.14715\/cmb\/2019.65.3.15","article-title":"Investigation of Cytotoxic, Genotoxic, and Apoptotic Effects of Curcumin on Glioma Cells","volume":"65","author":"Abdallah","year":"2019","journal-title":"Cell. Mol. Biol."},{"key":"ref_43","doi-asserted-by":"crossref","first-page":"9672773","DOI":"10.1155\/2022\/9672773","article-title":"Resveratrol Enhances the Radiosensitivity by Inducing DNA Damage and Antitumor Immunity in a Glioblastoma Rat Model under 3 T MRI Monitoring","volume":"2022","author":"Qian","year":"2022","journal-title":"J. Oncol."},{"key":"ref_44","doi-asserted-by":"crossref","unstructured":"Almatroodi, S.A., Alsahli, M.A., Aljohani, A.S.M., Alhumaydhi, F.A., Babiker, A.Y., Khan, A.A., and Rahmani, A.H. (2022). Potential Therapeutic Targets of Resveratrol, a Plant Polyphenol, and Its Role in the Therapy of Various Types of Cancer. Molecules, 27.","DOI":"10.3390\/molecules27092665"},{"key":"ref_45","doi-asserted-by":"crossref","first-page":"833","DOI":"10.17305\/bb.2024.11125","article-title":"Quercetin Regulates Sensitivity to X-Ray Radiation of Hepatocellular Carcinoma through MiR-216a-3p","volume":"25","author":"Bedolla","year":"2025","journal-title":"Biomol. Biomed."}],"container-title":["Cells"],"original-title":[],"language":"en","link":[{"URL":"https:\/\/www.mdpi.com\/2073-4409\/15\/16\/1484\/pdf","content-type":"unspecified","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2026,8,18]],"date-time":"2026-08-18T13:13:54Z","timestamp":1787058834000},"score":1,"resource":{"primary":{"URL":"https:\/\/www.mdpi.com\/2073-4409\/15\/16\/1484"}},"subtitle":[],"short-title":[],"issued":{"date-parts":[[2026,8,18]]},"references-count":45,"journal-issue":{"issue":"16","published-online":{"date-parts":[[2026,8]]}},"alternative-id":["cells15161484"],"URL":"https:\/\/doi.org\/10.3390\/cells15161484","relation":{},"ISSN":["2073-4409"],"issn-type":[{"value":"2073-4409","type":"electronic"}],"subject":[],"published":{"date-parts":[[2026,8,18]]}}}