An instrument-based screening assay for DNA-targeted anticancer drugs using resonance light scattering.
Comb Chem High Throughput Screen
; 13(5): 383-92, 2010 Jun.
Article
em En
| MEDLINE
| ID: mdl-20156144
ABSTRACT
DNA is a valid drug target for development of target-based therapeutics against cancer. Screening DNA-targeted anticancer drugs is a key process for the research and development of new anticancer drugs. The traditional anticancer drug screening methods, including animal experiments and cell-based screening assays, have unavoidable drawbacks. In this contribution, the new instrument-based screening assay for DNA-targeted anticancer drugs in vitro using resonance light scattering (RLS) technique was proposed. The experiments suggested that the increment of RLS intensity was directly proportional to the antitumor effect of anticancer drugs. Therefore, it was intuitive to obtain the sequence of the antitumor activity of four anticancer drugs without data processing as follows mitoxantrone (MIT) > pirarubicin (PIR) > daunorubicin (DAU) > doxorubicin (DOX) by RLS screening spectra. Moreover, the apparent equilibrium constant (K) was 1.23 x 10(4), 2.22 x 10(4), 4.66 x 10(4) L/mol for DOX, DAU, and PIR, respectively. The inhibitory concentration 50 (IC50) was 0.148, 0.102, 0.025, 0.013 micromol/L for DOX, DAU, PIR, MIT, respectively. Therefore, the antitumor effect of four drugs was as follows MIT > PIR > DAU > DOX, which was in good agreement with the result obtained from RLS screening assays. The mechanism between DNA and anthracycline drugs was investigated using UV-vis spectroscopy, fluorescence spectroscopy, and electrophoresis experiments. The proposed assay is a rapid, intuitive, and easy-to-conduct bioassay with good accuracy and reproducibility.
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Coleções:
01-internacional
Temas:
Geral
Base de dados:
MEDLINE
Assunto principal:
Espalhamento de Radiação
/
DNA
/
Ensaios de Seleção de Medicamentos Antitumorais
/
Ensaios de Triagem em Larga Escala
/
Luz
/
Antineoplásicos
Tipo de estudo:
Diagnostic_studies
/
Screening_studies
Limite:
Animals
/
Humans
Idioma:
En
Revista:
Comb Chem High Throughput Screen
Assunto da revista:
BIOLOGIA MOLECULAR
/
QUIMICA
Ano de publicação:
2010
Tipo de documento:
Article
País de afiliação:
China