J Cancer Prev.  2017 Mar;22(1):47-54. 10.15430/JCP.2017.22.1.47.

Non-homologous End Joining Inhibitor SCR-7 to Exacerbate Low-dose Doxorubicin Cytotoxicity in HeLa Cells

Affiliations
  • 1Cancer and Translational Research Lab, Dr. D.Y Patil Biotechnology & Bioinformatics Institute, Dr. D. Y. Patil Vidyapeeth, Pune, India. nilesh.sharma@dpu.edu.in

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.

Keyword

Carcinoma; Chemotherapy; DNA damage; DNA repair; Genomic instability

MeSH Terms

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
DNA
Doxorubicin
Propidium
Trypan Blue
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