DNA topoisomerases as additional targets for anticancer monofunctional platinum(ii) complexes

2021 ◽  
Vol 50 (1) ◽  
pp. 304-310
Author(s):  
Hongmei Zhang ◽  
Tao Yang ◽  
Yanqing Wang ◽  
Zenghui Wang ◽  
Zhenzhu Zhu ◽  
...  
Keyword(s):  
Dna Binding ◽  
Significant Inhibition ◽  
Mitochondrial Targeting ◽  
Dna Topoisomerases

Monofunctional platinum(ii) complexes show significant inhibition to DNA topoisomerases I/IIα besides DNA-binding and mitochondrial targeting capabilities, thereby potentiating the cytotoxicity.

scholarly journals Modified Gold Nanoparticles for Efficient Delivery of Betulinic Acid to Cancer Cell Mitochondria

2021 ◽  
Vol 22 (10) ◽  
pp. 5072
Author(s):  
Olakunle Oladimeji ◽  
Jude Akinyelu ◽  
Aliscia Daniels ◽  
Moganavelli Singh
Keyword(s):  
Polyethylene Glycol ◽  
Cancer Cell ◽  
Betulinic Acid ◽  
Targeted Delivery ◽  
Epigallocatechin Gallate ◽  
High Amplitude ◽  
Significant Inhibition ◽  
Mitochondrial Targeting ◽  
The Impact

Advances in nanomedicine have seen the adaptation of nanoparticles (NPs) for subcellular delivery for enhanced therapeutic impact and reduced side effects. The pivotal role of the mitochondria in apoptosis and their potential as a target in cancers enables selective induction of cancer cell death. In this study, we examined the mitochondrial targeted delivery of betulinic acid (BA) by the mitochondriotropic TPP+-functionalized epigallocatechin gallate (EGCG)-capped gold NPs (AuNPs), comparing the impact of polyethylene glycol (PEG) and poly-L-lysine-graft-polyethylene glycol (PLL-g-PEG) copolymer on delivery efficacy. This included the assessment of their cellular uptake, mitochondrial localization and efficacy as therapeutic delivery platforms for BA in the human Caco-2, HeLa and MCF-7 cancer cell lines. These mitochondrial-targeted nanocomplexes demonstrated significant inhibition of cancer cell growth, with targeted nanocomplexes recording IC50 values in the range of 3.12–13.2 µM compared to that of the free BA (9.74–36.31 µM) in vitro, demonstrating the merit of mitochondrial targeting. Their mechanisms of action implicated high amplitude mitochondrial depolarization, caspases 3/7 activation, with an associated arrest at the G0/G1 phase of the cell cycle. This nano-delivery system is a potentially viable platform for mitochondrial-targeted delivery of BA and highlights mitochondrial targeting as an option in cancer therapy.

DNA Binding by Fagaronine and Ethoxidine, Inhibitors of Human DNA Topoisomerases I and II, Probed by SERS and Flow Linear Dichroism Spectroscopy†

1999 ◽  
Vol 103 (11) ◽  
pp. 2008-2013 ◽  
Author(s):  
Anatoli Ianoul ◽  
Fabrice Fleury ◽  
Olivier Duval ◽  
Roger Waigh ◽  
Jean-Claude Jardillier ◽  
...  
Keyword(s):  
Dna Binding ◽  
Linear Dichroism ◽  
Dna Topoisomerases ◽  
Human Dna

Synthesis of Trifunctional PNA−Benzophenone Derivatives for Mitochondrial Targeting, Selective DNA Binding, and Photo-Cross-Linking

2003 ◽  
Vol 14 (5) ◽  
pp. 962-966 ◽  
Author(s):  
Günther F. Ross ◽  
Paul M. Smith ◽  
Alistair McGregor ◽  
Douglass M. Turnbull ◽  
Robert N. Lightowlers
Keyword(s):  
Dna Binding ◽  
Cross Linking ◽  
Mitochondrial Targeting ◽  
Selective Dna Binding

scholarly journals Inhibition of Nuclear Receptor Signalling by Poly(ADP-Ribose) Polymerase

1999 ◽  
Vol 19 (4) ◽  
pp. 2644-2649 ◽  
Author(s):  
Takahide Miyamoto ◽  
Tomoko Kakizawa ◽  
Kiyoshi Hashizume
Keyword(s):  
Dna Binding ◽  
Nuclear Receptor ◽  
Thyroid Hormone Receptor ◽  
Significant Inhibition ◽  
Binding Domain ◽  
Dna Binding Domain ◽  
Receptor Signalling ◽  
Defective Mutant ◽  
X Receptors

ABSTRACT Mammalian poly(ADP-ribose) polymerase (PARP) is a nuclear chromatin-associated protein with a molecular mass of 114 kDa that catalyzes the transfer of ADP-ribose units from NAD+ to nuclear proteins that are located within chromatin. We report here the identification of a novel property of PARP as a modulator of nuclear receptor signalling. PARP bound directly to retinoid X receptors (RXR) and repressed ligand-dependent transcriptional activities mediated by heterodimers of RXR and thyroid hormone receptor (TR). The interacting surface is located in the DNA binding domain of RXRα. Gel shift assays demonstrated that PARP bound to TR-RXR heterodimers on the response element. Overexpression of wild-type PARP selectively blocked nuclear receptor function in transient transfection experiments, while enzyme-defective mutant PARP did not show significant inhibition, suggesting that the essential role of poly(ADP-ribosyl) enzymatic activity is in gene regulation by nuclear receptors. Furthermore, PARP fused to the Gal4 DNA binding domain suppressed the transcriptional activity of the promoter harboring the Gal4 binding site. Thus, PARP has transcriptional repressor activity when recruited to the promoter. These results indicates that poly(ADP-ribosyl)ation is a negative cofactor in gene transcription, regulating a member of the nuclear receptor superfamily.

Histone H1–like protein participates in endothelial cell–specific activation of the von Willebrand factor promoter

Blood ◽  
2004 ◽  
Vol 104 (6) ◽  
pp. 1725-1732 ◽  
Author(s):  
Xinyu Wang ◽  
Yiwen Peng ◽  
Yuliang Ma ◽  
Nadia Jahroudi
Keyword(s):  
Transcription Factors ◽  
Endothelial Cell ◽  
Dna Binding ◽  
Von Willebrand Factor ◽  
Histone H1 ◽  
Specific Protein ◽  
Significant Inhibition ◽  
Protein Functions ◽  
Von Willebrand ◽  
Willebrand Factor

Abstract A region of the von Willebrand factor (VWF) promoter has been identified that is necessary to confer endothelial cell-specific activation to the VWF promoter. This region spans sequences +155 to +247 and contains binding sites for GATA6 and NFY transcription factors. To identify potential DNA binding transcription factors that directly interact with these sequences in an endothelial-specific manner, we have performed extensive gel mobility assays with use of 7 overlapping DNA probes that collectively span this entire region. An endothelial-specific protein DNA complex was formed with an oligonucleotide that corresponded to sequences +155 to +184 of the VWF gene. Mutation analysis identified a 6-nucleotide element corresponding to sequences +164 to +169 as the core-binding region for the formation of this complex. Transfection analysis demonstrated that the mutation, which abolished DNA-protein interaction, resulted in significant inhibition of the VWF promoter activity. DNA pull-down analysis, mass spectrometry, and Western blot analysis demonstrated that a 32-kDa polypeptide with homology to histone H1 constituted the endothelial-specific DNA binding protein, or a DNA binding subunit of this protein complex. On the basis of these results, we hypothesize that an H1-like protein functions as an endothelial cell-specific transcriptional activator of the VWF promoter. (Blood. 2004;104: 1725-1732)

Water soluble palladium(ii) and platinum(ii) acyclic diaminocarbene complexes: solution behavior, DNA binding, and antiproliferative activity

2020 ◽  
Vol 44 (15) ◽  
pp. 5762-5773 ◽  
Author(s):  
Tatiyana V. Serebryanskaya ◽  
Mikhail A. Kinzhalov ◽  
Vladimir Bakulev ◽  
Georgii Alekseev ◽  
Anastasiya Andreeva ◽  
...  
Keyword(s):  
Dna Binding ◽  
Antiproliferative Activity ◽  
Water Soluble ◽  
Solution Behavior ◽  
Antitumor Potential ◽  
Acyclic Diaminocarbene

Water soluble Pd(ii) and Pt(ii)–ADC species synthesized via the metal-mediated coupling of isocyanides and 1,2-diaminobenzene have demonstrated antitumor potential.

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