Quinones are naturally or synthetically occurring secondary metabolites that have various bio-dynamics, highlighting their antitumor potential. This has been explored through their selective cytotoxicity, and studies in medicinal chemistry about the relation between biological activity versus chemical structure may lead to the solution of the toxicity problems associated with quinones. In this context, the antitumor effect of a synthetic naphthoquinone, named Ethyl 2-(1,4-Dioxo-1,4-Dihydronaphthalen-2-Ylamino) Acetate, was tested using mice transplanted with Ehrlich ascitic tumor as an experimental model. The acute toxicity test was performed using 30 mice that received the aminoquinone at doses of 100, 200, 300, and 600 mg/kg. After evaluation of the clinical findings in the spontaneous activity tests, the LD50 calculation for the test substance showed low levels of toxicity at doses lower than 244.11 ± 23.29 mg/kg. Thus, three experimental groups were established, where animals transplanted with tumor cells received NaCl vehicle solution (control, n = 6), and the others were treated with 71.7 mg/kg of Methotrexate (n = 6) or 20 mg/kg of Aminoquinone (n = 6). All administrations were intraperitoneal, in a single dose. Three days after the implantation of the tumor cells the animals were weighed daily and evaluated for tumor biometry and development. The treatments occurred five days after the implantation of the tumor cells and were extended for 7 more days. At the end of the 12-day experimental period, all animals were euthanized for biochemical and histopathological analyses of the tumors and vital organs. The spontaneous activity test showed that the amount of responses associated with the nervous system tends to increase with the increase in dosage, highlighting the excitatory effect on the central nervous system in almost all dosages employed, followed by depressant activities on this system. There was a significant tumor reduction, both in animals treated with methotrexate (71.7 %) and in those treated with aminoquinone (91.6 %) in the control group. There was no significant difference in tumor volume between the animals treated with aminoquinone or methotrexate. The histopathological analysis revealed that in both treatments there were fewer mitoses in the tumor mass compared to the control group. However, there was apparent toxicity to the liver, heart, and left kidney in the treatment with methotrexate compared to aminoquinone. The significant capacity for tumor reduction presented by aminoquinone allows pointing it as a promising alternative for the development of a more efficient drug to control tumor development, being necessary for the development of new studies to deepen the knowledge about its mechanisms of action.
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http://dx.doi.org/10.1016/j.prp.2022.154272 | DOI Listing |
Cancer Cell Int
December 2024
Department of Applied Chemistry, Graduate Institute of Biomedicine and Biomedical Technology, National Chi Nan University, Puli, Taiwan.
Introduction: Chronic alcohol consumption and tobacco usage are major risk factors for esophageal squamous cell carcinoma (ESCC). Excessive tobacco and alcohol consumption lead to oxidative stress and the generation of reactive carbonyl species (RCS) which induce DNA damage and cell apoptosis. This phenomenon contributes to cell damage and carcinogenesis in various organs including ESCC.
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December 2024
Department of Maxillofacial and Otorhinolaryngology Oncology and Department of Head and Neck Oncology, Tianjin Medical University Cancer Institute and Hospital, Tianjin 300060, China; National Clinical Research Center for Cancer, Key Laboratory of Cancer Prevention and Therapy, Tianjin, China; Tianjin Key Laboratory of Basic and Translational Medicine on Head & Neck Cancer, Tianjin, China; Tianjin's Clinical Research Center for Cancer, Tianjin 300060, China. Electronic address:
Nerves are often overlooked as key components of the tumor microenvironment. However, the molecular mechanisms underlying the reciprocal interactions between tumors and nerves remain largely unknown. In this study, we analyzed data from The Cancer Genome Atlas (TCGA) and identified a significant association between DKK1 expression and poor prognosis, as well as a correlation between DKK1 expression and myeloid-derived suppressor cell (MDSC) infiltration in head and neck squamous cell carcinoma (HNSCC) and pancreatic ductal adenocarcinoma (PDAC), two cancer types characterized by pronounced tumor-nerve interactions.
View Article and Find Full Text PDFNat Cancer
December 2024
Department of Neurosurgery, Huashan Hospital, Shanghai Medical College, Fudan University, Shanghai, China.
The cerebrospinal fluid (CSF) border accommodates diverse immune cells that permit peripheral cell immunosurveillance. However, the intricate interactions between CSF immune cells and infiltrating cancer cells remain poorly understood. Here we use fate mapping, longitudinal time-lapse imaging and multiomics technologies to investigate the precise origin, cellular crosstalk and molecular landscape of macrophages that contribute to leptomeningeal metastasis (LM) progression.
View Article and Find Full Text PDFEur J Med Res
December 2024
Department of Gastrointestinal Surgery, Shandong Provincial Hospital, Shandong University, Jinan, 250021, Shandong, China.
The gut microbiota is a complex and dynamic ecosystem that plays a crucial role in human health and disease, including obesity, diabetes, cardiovascular diseases, neurodegenerative diseases, inflammatory bowel disease, and cancer. Chronic inflammation is a common feature of these diseases and is closely related to angiogenesis (the process of forming new blood vessels), which is often dysregulated in pathological conditions. Inflammation potentially acts as a central mediator.
View Article and Find Full Text PDFJ Nanobiotechnology
December 2024
GENYO, Centre for Genomics and Oncological Research, Pfizer/University of Granada/Andalusian Regional Government, PTS Granada, Avenida de la Ilustración, 18016, Granada, Spain.
MicroRNAs (miRNAs) have been recognised as potential biomarkers due to their specific expression patterns in different biological tissues and their changes in expression under pathological conditions. MicroRNA-122 (miR-122) is a vertebrate-specific miRNA that is predominantly expressed in the liver and plays an important role in liver metabolism and development. Dysregulation of miR-122 expression is associated with several liver-related diseases, including hepatocellular carcinoma and drug-induced liver injury (DILI).
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