Back to Search
Start Over
Substituted 3‑acyl‑2‑phenylamino‑1,4‑naphthoquinones intercalate into DNA and cause genotoxicity through the increased generation of reactive oxygen species culminating in cell death
- Source :
- Molecular medicine reports. 10(1)
- Publication Year :
- 2013
-
Abstract
- Naphthoquinones interact with biological systems by generating reactive oxygen species (ROS) that can damage cancer cells. The cytotoxicity and the antitumor activity of 3‑acyl‑2‑phenylamino‑1,4‑naphthoquinones (DPB1‑DPB9) were evaluated in the MCF7 human breast cancer cell line and in male Ehrlich tumor‑bearing Balb/c mice. DPB4 was the most cytotoxic derivative against MCF7 cells (EC50 15 µM) and DPB6 was the least cytotoxic one (EC50 56 µM). The 1,4‑naphthoquinone derivatives were able to cause DNA damage and promote DNA fragmentation as shown by the plasmid DNA cleavage assay (FII form). In addition, 1,4‑naphthoquinone derivatives possibly interacted with DNA as intercalating agents, which was demonstrated by the changes caused in the fluorescence of the DNA‑ethidium bromide complexes. Cell death of MCF7 cells induced by 3‑acyl‑2‑phenylamino‑1,4‑naphthoquinones was mostly due to apoptosis. The DNA fragmentation and subsequent apoptosis may be correlated to the redox potential of the 1,4‑naphthoquinone derivatives that, once present in the cell nucleus, led to the increased generation of ROS. Finally, certain 1,4‑naphthoquinone derivatives and particularly DPB4 significantly inhibited the growth of Ehrlich ascites tumors in mice (73%).
- Subjects :
- Male
Cancer Research
Programmed cell death
DNA damage
Transplantation, Heterologous
Antineoplastic Agents
Apoptosis
Biology
medicine.disease_cause
Biochemistry
Mice
Genetics
medicine
Animals
Humans
Carcinoma, Ehrlich Tumor
Molecular Biology
chemistry.chemical_classification
Reactive oxygen species
Mice, Inbred BALB C
DNA
Cell cycle
Molecular biology
Intercalating Agents
Oncology
chemistry
Cancer cell
MCF-7 Cells
Molecular Medicine
DNA fragmentation
Reactive Oxygen Species
Genotoxicity
DNA Damage
Naphthoquinones
Subjects
Details
- ISSN :
- 17913004
- Volume :
- 10
- Issue :
- 1
- Database :
- OpenAIRE
- Journal :
- Molecular medicine reports
- Accession number :
- edsair.doi.dedup.....6776f09d697f169124a108227aac7957