Journal of Cancer Prevention 2017; 22(1): 47-54
Published online March 30, 2017
© Korean Society of Cancer Prevention
Ajay Kumar, Devyani Bhatkar, Devashree Jahagirdar, and Nilesh Kumar Sharma
Cancer and Translational Research Lab, Dr. D.Y Patil Biotechnology & Bioinformatics Institute, Dr. D. Y. Patil Vidyapeeth, Pune, India
Correspondence to :
Nilesh Kumar Sharma, Cancer and Translation Research Group, Department of Biotechnology, Dr. D. Y. Patil Biotechnology & Bioinformatics Institute, Dr. D. Y Patil Vidyapeeth Pune, Pune, MH 411033, India Tel: +91-7219269540, Fax: +91-2067919444, E-mail: email@example.com, ORCID: Nilesh Kumar Sharma,
This is an Open Access article distributed under the terms of the Creative Commons Attribution Non-Commercial License (http://creativecommons.org/licenses/by-nc/4.0) which permits unrestricted non-commercial use, distribution, and reproduction in any medium, provided the original work is properly cited.
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.
Keywords: Carcinoma, Chemotherapy, DNA damage, DNA repair, Genomic instability
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