Genistein is a phytoestrogen that has shown potential as a chemotherapeutic agent, which acts by inhibiting protein-tyrosine kinase and topoisomerase II enzymes. These particular enzymes are crucial for cellular proliferation. The goal of this study was to evaluate the effect of genistein concentration (0.5, 0.05 or 0.005 mg/mL) on Hep-2 cells functional capacity. Specifically, to evaluate cellular number, protein, damage and morphology at 24, 48, and 72 hours phases. Data obtained from this study revealed that cell numbers were significantly reduced in low and medium concentrations after 24hrs, and cell numbers appeared to rebound at 48 and 72hrs in an inverse fashion. This data suggests continuous administration of the drug at therapeutic levels would serve as a better chemotherapeutic agent. Cellular damage was not evidenced and suggesting that the drug did not target the cellular membrane site. Morphological changes such as anucleation were seen at 24 hrs in all doses suggesting that genistein targets the genome directly. Interestingly, cellular function was able to recover in the lower doses of genistein treatment indicating cellular metabolism of the drug. Also, this information suggests that genistein mode of action by targeting enzymatic activity, as opposed to causing alterations within the cellular membrane, leading to leakage of cellular contents and ultimately cellular death since the membrane did not show evidence of lipid peroxidation.
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Oncoimmunology
December 2025
Earle A. Chiles Research Institute, Providence Cancer Institute, Portland, OR, USA.
Immune checkpoint blockade (ICB) has significantly improved the survival for many patients with advanced malignancy. However, fewer than 50% of patients benefit from ICB, highlighting the need for more effective immunotherapy options. High-dose interleukin-2 (HD IL-2) immunotherapy, which is approved for patients with metastatic melanoma and renal cell carcinoma, stimulates CD8 T cells and NK cells and can generate durable responses in a subset of patients.
View Article and Find Full Text PDFJ Am Chem Soc
January 2025
Department of Chemistry, Northwestern University, Evanston, Illinois 60208, United States.
The use of proteins as intracellular probes and therapeutic tools is often limited by poor intracellular delivery. One approach to enabling intracellular protein delivery is to transform proteins into spherical nucleic acid (proSNA) nanoconstructs, with surfaces chemically modified with a dense shell of radially oriented DNA that can engage with cell-surface receptors that facilitate endocytosis. However, proteins often have a limited number of available reactive surface residues for DNA conjugation such that the extent of DNA loading and cellular uptake is restricted.
View Article and Find Full Text PDFJ Am Chem Soc
January 2025
Department of Chemistry, University of California, Riverside, California 92521-0403, United States.
Pseudouridine (Ψ) is the most abundant RNA modification in nature; however, not much is known about the biological functions of this modified nucleoside. Employing an unbiased quantitative proteomics method, we identified multiple candidate reader proteins of Ψ in RNA, including a cytoskeletal protein profilin-1 (PFN1). We demonstrated that PFN1 binds directly and selectively to Ψ-containing RNA.
View Article and Find Full Text PDFCurr Pharm Biotechnol
January 2025
Department of Intensive Care Unit, Affiliated Hospital of Guangdong Medical University, 524000 Zhanjiang, China.
Objectives: This study aimed to comprehensively investigate the molecular landscape of gastric cancer (GC) by integrating various bioinformatics tools and experimental validations.
Methodology: GSE79973 dataset, limma package, STRING, UALCAN, GEPIA, OncoDB, cBioPortal, DAVID, TISIDB, Gene Set Cancer Analysis (GSCA), tissue samples, RT-qPCR, and cell proliferation assay were employed in this study.
Results: Analysis of the GSE79973 dataset identified 300 differentially expressed genes (DEGs), from which COL1A1, COL1A2, CHN1, and FN1 emerged as pivotal hub genes using protein-protein interaction network analysis.
CNS Neurol Disord Drug Targets
January 2025
Department of Biotechnology, National Institute of Technology, Raipur, 492001, India.
Parkinson's disease (PD) is a neurodegenerative disorder that results from the progressive loss of neurons in the brain followed by symptoms such as slowness and rigidity in movement, sleep disorders, dementia and many more. The different mechanisms due to which the neuronal degeneration occurs have been discussed, such as mutation in PD related genes, formation of Lewy bodies, oxidation of dopamine. This review discusses current surgical treatment and gene therapies with novel developments proposed for PD.
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