Different Effects of Cisplatin and Transplatin on the Higher-Order Structure of DNA and Gene Expression.
anticancer agent
cisplatin
gene expression
higher-order structure of DNA
platinum-based drug
single-molecule DNA observation
Journal
International journal of molecular sciences
ISSN: 1422-0067
Titre abrégé: Int J Mol Sci
Pays: Switzerland
ID NLM: 101092791
Informations de publication
Date de publication:
19 Dec 2019
19 Dec 2019
Historique:
received:
31
10
2019
revised:
15
12
2019
accepted:
17
12
2019
entrez:
22
12
2019
pubmed:
22
12
2019
medline:
6
5
2020
Statut:
epublish
Résumé
Despite the effectiveness of cisplatin as an anticancer agent, its trans-isomer, transplatin, is clinically ineffective. Although both isomers target nuclear DNA, there is a large difference in the magnitude of their biological effects. Here, we compared their effects on gene expression in an in vitro luciferase assay and quantified their effects on the higher-order structure of DNA using fluorescence microscopy (FM) and atomic force microscopy (AFM). The inhibitory effect of cisplatin on gene expression was about 7 times that of transplatin. Analysis of the fluctuation autocorrelation function of the intrachain Brownian motion of individual DNA molecules showed that cisplatin increases the spring and damping constants of DNA by one order of magnitude and these visco-elastic characteristics tend to increase gradually over several hours. Transplatin had a weaker effect, which tended to decrease with time. These results agree with a stronger inhibitory effect of cisplatin on gene expression. We discussed the characteristic effects of the two compounds on the higher-order DNA structure and gene expression in terms of the differences in their binding to DNA.
Identifiants
pubmed: 31861648
pii: ijms21010034
doi: 10.3390/ijms21010034
pmc: PMC6981875
pii:
doi:
Substances chimiques
transplatin
14913-33-8
DNA
9007-49-2
Cisplatin
Q20Q21Q62J
Types de publication
Comparative Study
Journal Article
Langues
eng
Sous-ensembles de citation
IM
Subventions
Organisme : Japan Society for the Promotion of Science
ID : 19K07018
Organisme : Japan Society for the Promotion of Science
ID : 15H02121
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