Toxicological ResearchPub Date : 2025-07-09eCollection Date: 2025-11-01DOI: 10.1007/s43188-025-00303-1
Hyejin Kim, Kwangsik Park
{"title":"Case study on the evaluation of skin sensitization for 23 selected fragrance ingredients using a defined approach based on OECD Guideline 497.","authors":"Hyejin Kim, Kwangsik Park","doi":"10.1007/s43188-025-00303-1","DOIUrl":"https://doi.org/10.1007/s43188-025-00303-1","url":null,"abstract":"<p><p>Twenty-three single-ingredient substances, selected from materials labeled as allergens in cosmetic fragrances, were assessed for skin sensitization potential using a defined approach (DA) based on the OECD Guideline 497 Integrated Testing Strategy version 2 (ITSv2). According to the ITSv2, skin hypersensitivity data for these selected substances were integrated. In chemico data (from the Direct Peptide Reactivity Assay, DPRA) and in vitro data (from the human Cell Line Activation Test, h-CLAT) were obtained from existing databases, while in silico data were generated via the automated workflow of the OECD QSAR Toolbox. The DA for skin sensitization, which combines QSAR predictions with DPRA and h-CLAT test results, categorized 17 substances, including 2-benzylideneheptanal, as \"Sensitizers\"; 5 substances, including 4-methoxybenzyl alcohol, as \"Inconclusive\"; and citronellol alone was categorized as \"Not Classified.\" The outcomes from the Local Lymph Node Assay (LLNA) for substances identified as skin sensitizers by the DA method demonstrated similar classification patterns to those from DA. These results underscore the necessity of integrating comprehensive in vitro, in chemico, and in silico data for accurate evaluation of potential skin sensitizers. This case study could aid in enhancing the safety assessments of potential skin sensitizers using DA; however, final categorization is subject to validation by regulatory authorities.</p>","PeriodicalId":23181,"journal":{"name":"Toxicological Research","volume":"41 6","pages":"601-610"},"PeriodicalIF":2.3,"publicationDate":"2025-07-09","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC12569283/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145410165","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":4,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
Toxicological ResearchPub Date : 2025-07-08eCollection Date: 2025-11-01DOI: 10.1007/s43188-025-00302-2
Khawaja Muhammad Imran Bashir, Hye-Ryeon An, Hyeyoung Shin, Joo Wan Kim, Jae-Suk Choi, Sae-Kwang Ku
{"title":"Oral toxicity evaluation of freeze-dried honeybee pupa powder (HDPp) in ICR mice: single-dose and 4-week repeated-dose studies.","authors":"Khawaja Muhammad Imran Bashir, Hye-Ryeon An, Hyeyoung Shin, Joo Wan Kim, Jae-Suk Choi, Sae-Kwang Ku","doi":"10.1007/s43188-025-00302-2","DOIUrl":"https://doi.org/10.1007/s43188-025-00302-2","url":null,"abstract":"<p><p>Drone pupae of honeybees (<i>Apis mellifera</i> L.) are rich in proteins, carbohydrates, fats, minerals, and vitamins, making them a valuable food ingredient in various regions including Korea, Japan, China, the United States, and parts of Europe. In this study, we investigated the safety of freeze-dried honeybee drone pupae (HDPp) as a potential functional food ingredient using single- and repeated-dose oral toxicity assessments. In the single-dose oral toxicity study, both male and female control groups were evaluated along with three test groups, each consisting of five animals, totaling 40 mice. The administered doses for the test groups were set at 2000, 1000, and 500 mg/kg body weight. The subjects were monitored over a period of 2 weeks following a single administration. Following the guidelines provided by the Korean Ministry of Food and Drug Safety, observations included mortality, changes in body weight, clinical symptoms, and post-mortem examinations of major organs for visual inspection and weight measurement. The repeated-dose oral toxicity study was extended over four weeks, employing the same dosages and methodology as the single-dose study. Additionally, this study incorporated blood and serological evaluations. The results demonstrated no toxicity-related effects in either single-dose or repeated-dose studies, suggesting that HDPp is a safe food ingredient with a lethal dose-50 exceeding 2000 mg/kg.</p>","PeriodicalId":23181,"journal":{"name":"Toxicological Research","volume":"41 6","pages":"581-599"},"PeriodicalIF":2.3,"publicationDate":"2025-07-08","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC12569256/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145410158","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":4,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
Toxicological ResearchPub Date : 2025-07-08eCollection Date: 2025-09-01DOI: 10.1007/s43188-025-00300-4
Young-Hun Kim, Da-Som Lee, Jung-Eum Lee, Heon Kim, Yong-Dae Kim, Young-Seoub Hong, Jung-Duck Park, Byung-Sun Choi
{"title":"Exposure and health effects follow-up study of residents near a former smelter site.","authors":"Young-Hun Kim, Da-Som Lee, Jung-Eum Lee, Heon Kim, Yong-Dae Kim, Young-Seoub Hong, Jung-Duck Park, Byung-Sun Choi","doi":"10.1007/s43188-025-00300-4","DOIUrl":"10.1007/s43188-025-00300-4","url":null,"abstract":"<p><p>The Seo-Cheon Janghang Smelter in South Korea closed in 1989 owing to its contribution to environmental pollution. The emissions from the smelter likely affect various environmental media and also pose significant health risks to nearby residents, particularly in relation to exposure to heavy metals such as lead, cadmium, and arsenic. Although the environmental impacts of the smelter are known, long-term follow-up studies on heavy metal exposure in nearby residents remain limited, especially after remediation. This study aimed to assess the levels of heavy metal exposure and associated health effects, particularly on renal and bone health. We analyzed blood and urine samples from 37 volunteers, collecting demographic, lifestyle, and exposure-related data through interviews. Renal function tests and bone mineral density measurements were conducted. The geometric means for blood lead (bPb) and blood cadmium (bCd) were 1.95 μg/dL and 2.68 μg/L, respectively. The mean urinary cadmium (uCd) concentration was 3.74 μg/g cr. Urinary total and harmful arsenic concentrations were 165.7 μg/L and 1.00 μg/L, respectively. The bPb levels significantly decreased from 2008 to 2020, whereas cadmium levels did not show significant change overall. Among 28 participants tested in both years, bCd levels decreased for individuals living > 2 km from the smelter, while remaining stable for those closer. The uCd levels significantly decreased only in individuals who had relocated > 2 km away from the smelter. Despite remediation efforts, uCd levels remain persistently elevated. These findings underscore the need for continuous exposure monitoring and longitudinal health assessments of residents living near the former smelter.</p>","PeriodicalId":23181,"journal":{"name":"Toxicological Research","volume":"41 5","pages":"523-532"},"PeriodicalIF":3.3,"publicationDate":"2025-07-08","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC12378821/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144970483","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":4,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
Toxicological ResearchPub Date : 2025-06-30eCollection Date: 2025-09-01DOI: 10.1007/s43188-025-00299-8
Hwa-Young Lee, Young Il Kim, Misong Kim, Bo-Hyung Kim, Sung-Vin Yim
{"title":"15-Deoxy-Δ<sup>12,14</sup>-prostaglandin J2 induces apoptosis in human microvascular endothelial cells (HMEC-1).","authors":"Hwa-Young Lee, Young Il Kim, Misong Kim, Bo-Hyung Kim, Sung-Vin Yim","doi":"10.1007/s43188-025-00299-8","DOIUrl":"10.1007/s43188-025-00299-8","url":null,"abstract":"<p><p>15-Deoxy-Δ<sup>12,14</sup>-prostaglandin J2 (15d-PGJ2) plays an important role in cell proliferation and apoptosis with various inhibitory effects. We investigated whether 15d-PGJ2 influence proliferation and apoptosis of human microvascular endothelial cells (HMEC-1), and suppression of the nuclear factor (NF)-κB activity and PI3K/AKT/mTOR signal pathway. Cell proliferation was analyzed using the MTS/PMS and colony formation assays. We analyzed the cell cycle using flow cytometry, while quantitative polymerase chain reaction (qPCR) measured mRNA expression, and immunoblot analysis quantified protein expression. 15d-PGJ2 inhibited cell growth and colony formation. In addition, it reduced the expression of cyclin-dependent kinase 4 and 6 (CDK4/6) and cyclin D1 mRNA but increased p21 mRNA expression. Apoptosis was increased during cell cycle progression and induced, as evident from the expression of apoptosis-related proteins, such as reduced Bcl-2 expression and increased Bax, caspase-3, and caspase-9 expression. Furthermore, the phosphorylation of NF-κB and PI3K/AKT/mTOR proteins was suppressed. This study found that 15d-PGJ2 inhibits cell proliferation, induces apoptosis, and regulates cell cycle- and apoptosis-related gene expression by suppressing the NF-κB and PI3K/AKT/mTOR pathways in HMEC-1 cells.</p>","PeriodicalId":23181,"journal":{"name":"Toxicological Research","volume":"41 5","pages":"515-522"},"PeriodicalIF":3.3,"publicationDate":"2025-06-30","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC12378245/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144970449","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":4,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
Toxicological ResearchPub Date : 2025-06-13eCollection Date: 2025-07-01DOI: 10.1007/s43188-025-00298-9
Xuan-Hung Nguyen, Jongman Yoo
{"title":"Current status and future prospects of toxicity assessment using organoids.","authors":"Xuan-Hung Nguyen, Jongman Yoo","doi":"10.1007/s43188-025-00298-9","DOIUrl":"10.1007/s43188-025-00298-9","url":null,"abstract":"<p><p>Organoids offer innovative platforms for toxicity assessment by more accurately recapitulating the structural and functional complexity of human tissues compared to traditional 2D cultures and animal models. This review summarizes current applications and discusses future directions for kidney, cardiac, liver, and brain organoids within the context of toxicology. Brain organoids, which recapitulate key features of human neural development, have facilitated investigations into neurotoxicity induced by agents such as Zika virus and chlorpyrifos. Kidney organoids, with nephron-like structures, have been employed to model nephrotoxicity induced by chemotherapeutic agents. Cardiac organoids, which mimic heart contractions and electrical properties, are effective for assessing cardiotoxicity from drugs such as doxorubicin. Liver organoids allow prediction of hepatotoxicity through the modeling of human-specific drug metabolism, as shown in studies using compounds like acetaminophen and troglitazone. Despite their promise, organoid systems still face challenges such as cellular immaturity, batch-to-batch variability, and limited vascularization. Emerging technologies such as 3D bioprinting, vascular integration, and multi-organ assembly are expected to improve the applicability of organoids in toxicity testing. Additionally, integration with microfluidic platforms and artificial intelligence-based analysis will improve high-throughput screening and predictive accuracy. As these technologies continue to evolve, organoids are poised to play a critical role in safer drug development, reducing dependence on animal models and providing deeper insights into systemic toxicity.</p>","PeriodicalId":23181,"journal":{"name":"Toxicological Research","volume":"41 4","pages":"325-333"},"PeriodicalIF":3.3,"publicationDate":"2025-06-13","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC12214188/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144561259","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":4,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
{"title":"Chemically-induced histopathological progression in the polycystic ovary syndrome (PCOS)- A review.","authors":"Mehjbeen Javed, Suramya, Shahzad Ahmad, Sheikh Raisuddin","doi":"10.1007/s43188-025-00296-x","DOIUrl":"10.1007/s43188-025-00296-x","url":null,"abstract":"<p><p>Polycystic ovary syndrome (PCOS) is the most common endocrine-gynecological disorder, affecting 4-10% of women of reproductive age. Although a fragment of the involved mechanism behind the PCOS occurrence is discovered, the exact etiology and pathophysiology are not completely understood yet. The pathogenesis of the disease involves several genetic, epigenetic, and environmental factors, as well as poor lifestyle. Chemicals that interact adversely with the endocrine glands are ubiquitous in the ecosystem and are known as endocrine-disrupting chemicals. An exposed population, especially women at a growing age, undergoes many hormonal and physiological changes and is more susceptible to developing endocrinological disorders like PCOS. An effective diagnosis of the disease can be made by observing changes in cells that are associated with the progression of the disease. Histopathological changes provide abundant evidence that is directly or indirectly involved in its progression and help in the evaluation of the complexity of the disease. In case of environmental stress, the body responds via some visible changes in cells, including the position and size of small cysts, changes in atretic follicles and ovarian capsules, thickening of ovarian tunica, and increased intra-ovarian cysts are some of the examples that are involved in etiology of disease. Therefore, in this review, we will try to understand the progression of PCOS by observing morphological changes through the histopathology of associated tissues that can be a plausible predictor of malignant changes in the disease. Our primary aim is to summarize the existing literature of experiments and contribute to a better understanding of the disease and associated problems.</p>","PeriodicalId":23181,"journal":{"name":"Toxicological Research","volume":"41 5","pages":"437-453"},"PeriodicalIF":3.3,"publicationDate":"2025-05-21","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC12378891/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144970468","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":4,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
Toxicological ResearchPub Date : 2025-05-20eCollection Date: 2025-09-01DOI: 10.1007/s43188-025-00297-w
Hayoung Lee, Byungkyung Do, Hoonjeong Kwon
{"title":"Effect of red yeast rice on the growth of male SD rats: a 90-day feeding study.","authors":"Hayoung Lee, Byungkyung Do, Hoonjeong Kwon","doi":"10.1007/s43188-025-00297-w","DOIUrl":"10.1007/s43188-025-00297-w","url":null,"abstract":"<p><p>Red yeast rice (RYR) is commonly used as colouring and flavouring agent in foods throughout East Asia. RYR contains monacolin K, a compound known to lower blood lipids level, which has led to its use as a health functional food in Korea. Additionally, RYR is frequently used as a food ingredient and is incorporated into processed foods such as bread and makgeolli, a traditional Korean alcoholic beverage. However adverse effects associated with RYR have been reported by several regulatory agencies, prompting the need for further investigation of its safety as a general food ingredient. To evaluate its safety, a 90-day feeding study was conducted using Sprague-Dawley (SD) rats, which were randomly assigned to three experimental groups. The experimental diets were prepared by replacing the corn starch in AIN 93G with RYR and/or white rice. Rats fed RYR showed lower body weight gain, accompanied by reduced food efficiency. No signs of toxicity were observed in serum clinical chemistry, relative organ weights, or histopathological analysis. However, hyperplasia and hypertrophy were observed in the thyroid, although the cause remained unclear. These results suggest that RYR exhibits a very low toxic potential, if any. Nevertheless, caution is advised regarding its expanded use, particularly among younger population, due to its growing inhibitory effects.</p>","PeriodicalId":23181,"journal":{"name":"Toxicological Research","volume":"41 5","pages":"503-513"},"PeriodicalIF":3.3,"publicationDate":"2025-05-20","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC12378799/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144970528","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":4,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
Toxicological ResearchPub Date : 2025-05-19eCollection Date: 2025-09-01DOI: 10.1007/s43188-025-00287-y
Hye-Jeong Sin, Ji-Young Bae, Sun-A Cho, Minseok Choi, Changwan Ha, Chang Eon Park, Jeong-Ja Oh, Susun An, Bae-Hwan Kim
{"title":"Validation study of spectrophotometric direct peptide reactivity assay (spectro-DPRA), a newly modified in chemico skin sensitization test method.","authors":"Hye-Jeong Sin, Ji-Young Bae, Sun-A Cho, Minseok Choi, Changwan Ha, Chang Eon Park, Jeong-Ja Oh, Susun An, Bae-Hwan Kim","doi":"10.1007/s43188-025-00287-y","DOIUrl":"10.1007/s43188-025-00287-y","url":null,"abstract":"<p><p>This study was conducted to evaluate the accuracy and reliability of the Spectro-DPRA, an enhanced method for the OECD TG 442C (direct peptide reactivity assay, DPRA), serving as an alternative to animal testing for skin sensitization. The validation of Spectro-DPRA was executed across four participating laboratories (Lab 1, Lab 2, Lab 3, and Lab 4, the latter only participating in the proficiency test) adhering to GLP principles. It covered transferability, proficiency, within laboratory and between laboratory reproducibility tests, and a predictive capacity test using 40 additional substances. In tests with 10 proficiency substances, results from all participating laboratories fell within the respective reference ranges for 8 of the 10 substances for each peptide. The within laboratory reproducibility for 12 test substances demonstrated success rates of 83.3% for both Lab 1 and Lab 3, and 100% for Lab 2. The between laboratory reproducibility for 20 test substances showed an 85% concordance rate. The predictive capacity for these substances did not align with the test method similarity criteria stipulated in the OECD Series on Testing and Assessment No. 303 (performance standards for the assessment of proposed similar or modified in vitro skin sensitisation DPRA and ADRA test methods, OECD PS No.303), with accuracy, sensitivity, and specificity rates at 74.6%, 70.9%, and 81.4%, respectively. However, the predictive capacity for an additional 40 substances revealed high accuracy (85.2%), sensitivity (82.2%), and specificity (97.0%). Although the Spectro-DPRA did not completely conform to the OECD PS No.303 criteria for test method similarity, it showed high predictive accuracy of over 80% for the 40 additional substances, confirming its reliability as a test method for skin sensitization evaluation.</p>","PeriodicalId":23181,"journal":{"name":"Toxicological Research","volume":"41 5","pages":"455-475"},"PeriodicalIF":3.3,"publicationDate":"2025-05-19","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC12378800/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144970538","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":4,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
Toxicological ResearchPub Date : 2025-05-16eCollection Date: 2025-09-01DOI: 10.1007/s43188-025-00295-y
Hafithe M AlGhosain, Jiarui Nie, Tao Liu, Jonghwan Lee
{"title":"The systemic toxicity of intravitreally injected gold nanorods in mice: Effects of size, surface conjugation, and post-injection period.","authors":"Hafithe M AlGhosain, Jiarui Nie, Tao Liu, Jonghwan Lee","doi":"10.1007/s43188-025-00295-y","DOIUrl":"10.1007/s43188-025-00295-y","url":null,"abstract":"<p><p>Gold nanorods (AuNRs) are promising for remote neuronal activation via photothermal effects, but their systemic toxicity when delivered ocularly is unclear. We assessed the systemic safety of intravitreally injected AuNRs in mice over 32 days, testing three formulations: 25-nm diameter Thy-1 conjugated AuNRs (default), 10-nm diameter Thy-1 conjugated AuNRs (effect of size), and 25-nm diameter bare AuNRs (effect of surface chemistry). Thy-1 conjugation aimed to target retinal neurons specifically. Mice received AuNR injections or phosphate-buffered saline as a control. Hematological parameters, serum biochemistry, and body weight were evaluated at 2-, 8-, and 32-days post-injection. Thy-1 conjugated AuNRs did not significantly alter serum biochemical indices or blood counts compared to controls, indicating no systemic toxicity. In contrast, mice injected with bare AuNRs showed a 23% increase in uric acid levels (<i>p</i> = 0.0018), suggesting potential systemic effects due to lack of targeted delivery. Age influenced monocyte concentration, and cholesterol level, while sex differences were noted in body weight and several hematological and biochemical parameters. Our findings suggest that intravitreally injected Thy-1 conjugated AuNRs are systemically safe up to 32 days post-injection, emphasizing the importance of targeted nanoparticle design to mitigate potential toxicity.</p><p><strong>Graphical abstract: </strong></p>","PeriodicalId":23181,"journal":{"name":"Toxicological Research","volume":"41 5","pages":"489-502"},"PeriodicalIF":3.3,"publicationDate":"2025-05-16","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC12378798/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144970454","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":4,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
Toxicological ResearchPub Date : 2025-05-13eCollection Date: 2025-09-01DOI: 10.1007/s43188-025-00293-0
Yun-Hee Jeoung, Hong Kyu Lee, Seung-Hyeon Ahn, Zeeshan Ahmad Bhutta, Kyung-Chul Choi
{"title":"Tangeretin induces apoptosis and cell cycle arrest in thyroid cancer cells.","authors":"Yun-Hee Jeoung, Hong Kyu Lee, Seung-Hyeon Ahn, Zeeshan Ahmad Bhutta, Kyung-Chul Choi","doi":"10.1007/s43188-025-00293-0","DOIUrl":"10.1007/s43188-025-00293-0","url":null,"abstract":"<p><p>Thyroid cancer is a malignant tumor whose incidence is increasing worldwide. While thyroid cancer is treatable and curable, a small number of cases can become metastatic when cancer cells originating in the thyroid gland spread to other parts of the body through the bloodstream or lymphatic system. The most common treatments for thyroid cancer are resection and radioactive iodine therapy. However, these treatments have side effects, such as hypothyroidism and damage to normal non-cancerous cells. Tangeretin is a polymethoxylated flavone found in the peel of citrus plants and has biological activity, including antioxidant, anti-inflammatory, and anti-cancer effects. However, the effects of tangeretin on human thyroid cancer have not been investigated. In this study, the effects of tangeretin on cell proliferation and apoptosis of the thyroid cancer cell line SNU-790 were investigated. To prove the results of this study, A water-soluble tetrazolium salt (WST) assay, cell cycle arrest assay, annexin V/PI, DCF-DA, JC-10, and western blot were used. Treatment with tangeretin decreased SNU-790 cell viability and proliferation ability. Annexin V/PI staining showed that tangeretin increased apoptotic cell death. In the wound healing assay, the tangeretin treatment decreased the wound closure area. In addition, tangeretin treatment increased the level of reactive oxygen species (ROS) in the cytosolic of SNU-790. The JC-10 assay showed that the tangeretin treatment decreased the mitochondrial membrane potential (MMP). Western blot analysis revealed that treatment with tangeretin increased the expression of the tumor protein p53. In conclusion, these results indicated that tangeretin inhibited the progression of thyroid cancer in SNU-790 cells by inhibiting migration ability, inducing mitochondrial dysfunction, and mediating oxidative stress in SNU-790. Hence, this study provides experimental evidence that tangeretin could be a potential candidate for the management of thyroid cancer.</p>","PeriodicalId":23181,"journal":{"name":"Toxicological Research","volume":"41 5","pages":"477-488"},"PeriodicalIF":3.3,"publicationDate":"2025-05-13","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC12379201/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144970522","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":4,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}