Troxerutin, a flavonoid best known for its radioprotective and antioxidant properties is of considerable interest of study due to its broad pharmacological activities. The present study on troxerutin highlights its abilities to bind DNA and enhance cancer cell killing in response to radiation. Troxerutin showed strong binding with calf thymus DNA in vitro. Troxerutin-DNA interaction was confirmed by CD spectropolarimetry. The mode of binding of troxerutin to DNA was assessed by competing troxerutin with EtBr or DAPI, known DNA intercalator and a minor groove binder, respectively. DAPI fluorescence was drastically reduced with linear increase in troxerutin concentration suggesting possible binding of troxerutin to DNA minor groove. Further, computational studies of docking of troxerutin molecule on mammalian DNA also indicated possible troxerutin-DNA interaction at minor groove of DNA. Troxerutin was found to mainly localize in the nucleus of prostate cancer cells. It induced cytotoxicity in radioresistant (DU145) and sensitive (PC3) prostate cancer cells. When troxerutin pre-treated DU145 and PC3 cells were exposed to γ-radiation, cytotoxicity as estimated by MTT assay, was found to be further enhanced. In addition, the % subG1 population detected by propidium iodide staining also showed similar response when combined with radiation. A similar trend was observed in terms of ROS generation and DNA damage in DU145 cells when troxerutin and radiation were combined. DNA binding at minor groove by troxerutin may have contributed to strand breaks leading to increased radiation induced cell death.
Download full-text PDF |
Source |
|---|---|
| http://dx.doi.org/10.1016/j.cbi.2016.03.024 | DOI Listing |
Publication Analysis
Top Keywords
Similar Publications
MGB probe-based multiplex droplet digital PCR for the interspecific identification of Notopterygii Rhizoma et Radix in herbal materials and preparations.
Phytomedicine
December 2024
State Key Laboratory of Drug Regulatory Science, Beijing 102629, China; Chinese Pharmacopoeia Commission, Beijing 100061, China. Electronic address:
Background: Owing to high sensitivity and ability for absolute quantification, the droplet digital polymerase chain reaction (ddPCR) is widely used for viral and bacterial detection. However, few studies have been conducted on the application of ddPCR to identify the original plant species used in traditional Chinese medicine and Chinese patent medicine.
Purpose: In this study, we investigated the feasibility of using ddPCR to differentiate between Notopterygium incisum and N.
Investigation of the impact of R273H and R273C mutations on the DNA binding domain of P53 protein through molecular dynamic simulation.
J Biomol Struct Dyn
February 2025
Laboratory of Integrative Genomics, Department of Integrative Biology, School of Bio Sciences and Technology, Vellore Institute of Technology (VIT), Vellore, India.
The P53 protein, a cancer-associated transcriptional factor and tumor suppressor, houses a Zn ion in its DNA-binding domain (DBD), essential for sequence-specific DNA binding. However, common mutations at position 273, specifically from Arginine to Histidine and Cysteine, lead to a loss of function as a tumor suppressor, also called DNA contact mutations. The mutant (MT) P53 structure cannot stabilize DNA due to inadequate interaction.
View Article and Find Full Text PDFHistone N-tails modulate sequence-specific positioning of nucleosomes.
J Biol Chem
December 2024
National Cancer Institute, National Institutes of Health, Bethesda, MD 20892, USA. Electronic address:
Spatial organization of chromatin is essential for cellular functioning. However, the precise mechanisms governing sequence-dependent positioning of nucleosomes on DNA still remain unknown in detail. Existing algorithms, taking into account the sequence-dependent deformability of DNA and its interactions with the histone globular domains, predict rotational setting of only 65% of human nucleosomes mapped in vivo.
View Article and Find Full Text PDFStructural investigation of erdafitinib, an anticancer drug, with ctDNA: A spectroscopic and computational study.
Biochim Biophys Acta Gen Subj
December 2024
Department of Biochemistry, Faculty of Life Sciences, Aligarh Muslim University, Aligarh 202002, India. Electronic address:
The interaction of drugs with DNA is crucial for understanding their mechanism of action, particularly in the context of gene expression regulation. Erdafitinib (EDB), a pan-FGFR (fibroblast growth factor receptor) inhibitor approved by the FDA, is a potent anticancer agent used primarily in the treatment of urothelial carcinoma. In this study, the binding interaction between EDB and calf thymus DNA (ctDNA) was assessed using molecular docking, UV-absorption spectroscopy, fluorescence spectroscopy, and circular dichroism (CD) spectroscopy.
View Article and Find Full Text PDFSequence-Specific Minor Groove Binders in Labeling and Single-Molecule Analysis of DNA.
J Am Chem Soc
December 2024
Department of Chemistry, KU Leuven, Leuven 3001, Belgium.
The ability to address specific sequences within DNA is of tremendous interest in biotechnology and biomedicine. Various technologies have been established over the past few decades, such as nicking enzymes and methyltransferase-directed sequence-specific labeling, transcription activator-like effector nucleases (TALENs), the CRISPR-Cas9 system, and polyamides of heterocycles as sequence-specific DNA minor groove binders. Pyrrole-imidazole polyamides have been reported to recognize predetermined DNA sequences, and some successful attempts have demonstrated their potential in regulating gene expression.
View Article and Find Full Text PDFWant AI Summaries of new PubMed Abstracts delivered to your In-box?
Enter search terms and have AI summaries delivered each week - change queries or unsubscribe any time!