The interaction of cisplatin and analogues with DNA in reconstituted chromatin

Galea, Anne M.; Murray, Vincent

doi:10.1016/s0167-4781(02)00535-3

Cited by 50 publications

(28 citation statements)

References 36 publications

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“…Of note, this SNP was previously reported by our lab in association with carboplatin susceptibility in LCLs from individuals representing multiple ethnicities 15, and importantly, this SNP was highly associated with the baseline expression (at least in Asian individuals’ LCLs) of HIST1H3A , a gene in the histone family which has logical mechanistic and demonstrated relevance for regulating platinum-adduct formation on DNA 29, 30. The potential association of this SNP with hematologic changes in HNC patients receiving carboplatin-based chemotherapy further increases its interest as a potentially important pharmacogenomic determinant.…”

Section: Discussionsupporting

confidence: 58%

Germline polymorphisms discovered via a cell-based, genome-wide approach predict platinum response in head and neck cancers

Ziliak

O’Donnell

et al. 2011

Translational Research

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Identifying patients prior to treatment who are more likely to benefit from chemotherapeutic agents or more likely to experience adverse events is the aim of personalized medicine. Pharmacogenomics offers a potential means of achieving this through the discovery of predictive germline genetic biomarkers. When applied particularly to the treatment of head and neck cancers, such information could offer significant benefit to patients as a means of potentially reducing morbidity associated with platinum-based chemotherapy. We developed a genome-wide cell-based approach to identify single nucleotide polymorphisms (SNPs) associated with platinum susceptibility and then evaluated these SNPs as predictors for response and toxicity in head and neck cancer patients treated with platinum-based therapy as part of a phase II clinical trial. Sixty head and neck cancer patients were evaluated. Of 45 genome-wide SNPs examined, we found that two SNPs, rs6870861 (p=0.004; false discovery rate [FDR] <0.05) and rs2551038 (p=0.005; FDR <0.05), were significantly associated with overall response to carboplatin-based induction chemotherapy when incorporated into a model along with total carboplatin exposure. Interestingly, these two SNPs are strongly associated with the baseline expression of ≥20 genes (all p≤10 −4 ) and two of the genes (SLC22A5 and SLCO4C1) are important organic cation/anion transporters known to affect platinum uptake and clearance. Several other SNPs were nominally associated with carboplatin-related hematologic toxicities. These findings importantly demonstrate that a genomewide cell-based model can identify novel germline genetic biomarkers of platinum susceptibility © 2011 Mosby, Inc. All rights reserved. * Address for correspondence and reprints: R. Stephanie Huang, 900 E 57 th Street, KCBD room 7148, The University of Chicago, Chicago, IL 60637. Phone: (773) 702-9363; Fax: (773) 702-0963; rhuang@medicine.bsd.uchicago.edu. § these authors contributed equally to the work Publisher's Disclaimer: This is a PDF file of an unedited manuscript that has been accepted for publication. As a service to our customers we are providing this early version of the manuscript. The manuscript will undergo copyediting, typesetting, and review of the resulting proof before it is published in its final citable form. Please note that during the production process errors may be discovered which could affect the content, and all legal disclaimers that apply to the journal pertain.The authors have no potential conflicts of interest to declare. The authors did not use editorial support for preparation of the manuscript. NIH Public Access

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Section: Discussionsupporting

confidence: 58%

Germline polymorphisms discovered via a cell-based, genome-wide approach predict platinum response in head and neck cancers

Ziliak

O’Donnell

et al. 2011

Translational Research

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“…In fact, the slightly higher fraction of both RAED-C and RAPTA-C adducts associated with the DNA for the cellular chromatin analysis suggests a greater reactivity of the protein-free, or linker, DNA that connects adjacent nucleosome core regions in the genome (see below)—a phenomenon that has been found for platinum drugs and other types of small molecules1118.…”

Section: Resultsmentioning

confidence: 94%

Ligand substitutions between ruthenium–cymene compounds can control protein versus DNA targeting and anticancer activity

et al. 2014

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Ruthenium compounds have become promising alternatives to platinum drugs by displaying specific activities against different cancers and favourable toxicity and clearance properties. Nonetheless, their molecular targeting and mechanism of action are poorly understood. Here we study two prototypical ruthenium-arene agents—the cytotoxic antiprimary tumour compound [(η6-p-cymene)Ru(ethylene-diamine)Cl]PF6 and the relatively non-cytotoxic antimetastasis compound [(η6-p-cymene)Ru(1,3,5-triaza-7-phosphaadamantane)Cl2]—and discover that the former targets the DNA of chromatin, while the latter preferentially forms adducts on the histone proteins. Using a novel ‘atom-to-cell’ approach, we establish the basis for the surprisingly site-selective adduct formation behaviour and distinct cellular impact of these two chemically similar anticancer agents, which suggests that the cytotoxic effects arise largely from DNA lesions, whereas the protein adducts may be linked to the other therapeutic activities. Our study shows promise for developing new ruthenium drugs, via ligand-based modulation of DNA versus protein binding and thus cytotoxic potential, to target distinguishing epigenetic features of cancer cells.

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“…Moreover, cisplatin-induced tubular damage could be explained by the fact that, as fast as cisplatin is in the interior of the cells, the hydrolysis product (chloride atoms replaced by water molecules) reacts with GSH in the cytoplasm and DNA in the nucleus [42]. The produced cisplatin-DNA intrastrand cross-links result in cytotoxicity (apoptosis/ necrosis) [43].…”

Section: Discussionmentioning

confidence: 99%

Comparative Study of the Possible Protective Effects of Cinnamic Acid and Cinnamaldehyde on Cisplatin-Induced Nephrotoxicity in Rats

El-Sayed

El‐Raouf

Fawzy

et al. 2013

J Biochem Mol Toxicol

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This study aimed to assess the protective effect of cinnamic acid (CA) and cinnamaldehyde (CD) against cisplatin-induced nephrotoxicity. A single dose of cisplatin (5 mg/kg), injected intraperitoneally to male rats, caused significant increases in serum urea, creatinine levels, and lipid peroxides measured as the malondialdehyde content of kidney, with significant decreases in serum albumin, reduced glutathione, and the activity of antioxidant enzymes (catalase, superoxide dismutase, and glutathione peroxidase) of kidney as compared with the control group. On the other hand, administration of CA (50 mg/kg, p.o.) or CD (40 mg/kg, p.o.) for 7 days before cisplatin ameliorated the cisplatin-induced nephrotoxicity as indicated by the restoration of kidney function and oxidative stress parameters. Furthermore, they reduced the histopathological changes induced by cisplatin. In conclusion, CA and CD showed protective effects against cisplatin-induced nephrotoxicity where CD was more effective than CA; affects that might be attributed to their antioxidant activities.

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The interaction of cisplatin and analogues with DNA in reconstituted chromatin

Cited by 50 publications

References 36 publications

Germline polymorphisms discovered via a cell-based, genome-wide approach predict platinum response in head and neck cancers

Germline polymorphisms discovered via a cell-based, genome-wide approach predict platinum response in head and neck cancers

Ligand substitutions between ruthenium–cymene compounds can control protein versus DNA targeting and anticancer activity

Comparative Study of the Possible Protective Effects of Cinnamic Acid and Cinnamaldehyde on Cisplatin-Induced Nephrotoxicity in Rats

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