Non-homologous End Joining Inhibitor SCR-7 to Exacerbate Low-dose Doxorubicin Cytotoxicity in HeLa Cells.
10.15430/JCP.2017.22.1.47
- Author:
Ajay KUMAR
1
;
Devyani BHATKAR
;
Devashree JAHAGIRDAR
;
Nilesh Kumar SHARMA
Author Information
1. Cancer and Translational Research Lab, Dr. D.Y Patil Biotechnology & Bioinformatics Institute, Dr. D. Y. Patil Vidyapeeth, Pune, India. nilesh.sharma@dpu.edu.in
- Publication Type:Original Article
- Keywords:
Carcinoma;
Chemotherapy;
DNA damage;
DNA repair;
Genomic instability
- MeSH:
Cell Death;
DNA;
DNA Damage;
DNA End-Joining Repair;
DNA Repair;
Doxorubicin*;
Drug Therapy;
Genomic Instability;
HeLa Cells*;
Humans;
In Vitro Techniques;
Plasmids;
Propidium;
Trypan Blue;
Uterine Cervical Neoplasms
- From:Journal of Cancer Prevention
2017;22(1):47-54
- CountryRepublic of Korea
- Language:English
-
Abstract:
Among the genotoxic drug regimens, doxorubicin (DOX) is known for its high-dose side effects in several carcinomas, including cervical cancer. This study reports on testing the combined use of a DOX genotoxic drug and SCR-7 non-homologous end joining (NHEJ) inhibitor for HeLa cells. An in vitro DNA damaging assay of DOX was performed on plasmid and genomic DNA substrate. In vitro cytotoxicity was investigated using trypan blue dye exclusion, DNA metabolizing, and propidium iodide-based flow cytometric assays. DOX (between 20–100 μM) displayed clear DNA binding and interaction, such as the shearing and smearing of plasmid and genomic DNA. DNA metabolizing assay data indicate that HeLa lysate with DOX and SCR-7 treatment exhibited better in vitro plasmid DNA stability compared with DOX treatment alone. SCR-7 augmented the effects of low-dose DOX by demonstrating enhanced cell death from 15% to 50%. The flow cytometric data also supported that the combination of SCR-7 with DOX lead to a 23% increase in propidium iodide-based HeLa staining, thus indicating enhanced death. In summary, the inhibition of NHEJ DNA repair pathway can potentiate low-dose DOX to produce appreciable cytotoxicity in HeLa cells.
