• Users Online: 743
  • Home
  • Print this page
  • Email this page
Home About us Editorial board Ahead of print Current issue Search Archives Submit article Instructions Subscribe Contacts Login 
Year : 2018  |  Volume : 9  |  Issue : 2  |  Page : 93-101

Inhibitor of nonhomologous end joining can inhibit proliferation of diffuse large B-Cell lymphoma cells and potentiate the effect of ionization radiation

1 Institute of Bioinformatics and Applied Biotechnology; Department of Biochemistry, n Institute of Science, Bengaluru; Manipal Academy of Higher Education, Manipal, Karnataka, India
2 Department of Biochemistry, n Institute of Science, Bengaluru, Karnataka, India
3 sInstitute of Bioinformatics and Applied Biotechnology, Bengaluru, Karnataka, India

Correspondence Address:
Dr. Bibha Choudhary
Institute of Bioinformatics and Applied Biotechnology, Bengaluru, Karnataka
Login to access the Email id

Source of Support: None, Conflict of Interest: None

DOI: 10.4103/jrcr.jrcr_9_18

Rights and Permissions

Aim: Diffuse large B-cell lymphoma (DLBCL) is the most common and aggressive type of non-Hodgkin's lymphoma that accounts for ~40% of all lymphomas. DLBCL is considered to be clinically heterogeneous with highest mortality rate. Recent advances in gene expression profiling helped in identifying different subtypes of DLBCL, and since then, many therapeutic options have been explored to treat DLBCL patients. Although it is effective, a significant proportion of the patients suffer due to drug resistance. One of the potential causes for this could be elevated DNA repair in the resistant cancer cells. Thus, the present study is aimed at investigating the potential of SCR7, a DNA repair inhibitor in inducing cytotoxicity on a DLBCL cell line, and to study its ability to potentiate effect when used in combination with ionizing radiation. Materials and Methods: DLBCL cell line, Standford University Diffuse Histiocytic Lymphoma 8 (SUDHL8) was treated with various concentrations of SCR7, a DNA repair inhibitor that targets nonhomologous DNA end joining. While cytotoxicity induced by SCR7 was evaluated through trypan blue assay and flow cytometry analysis, 5,5',6,6 tetrachloro-1,1',3,3'-tetraethyl benzimidazol-carbocyanine iodide and annexin V-FITC/propidium iodide [PI] double-staining assays were used to study the mechanism of cell death. Modulation in the level of DNA repair and apoptotic proteins following treatment with SCR7 was examined by immunoblotting. Effect of SCR7 on sensitizing radiotherapy was further investigated in the SUDHL8 cells. Results: SCR7 induced cytotoxicity in the DLBCL cell line in a concentration- and time-dependent manner. Cell cycle analysis and annexin V/PI double-staining assay confirmed apoptosis in cells without interfering with cell cycle progression. Change in mitochondrial membrane potential in conjunction with alterations in the levels of apoptotic proteins suggested activation of both intrinsic and extrinsic pathways of apoptosis. Importantly, administration of SCR7 potentiated the effect of radiation upon combination therapy in DLBCL. Conclusion: Our results suggest that SCR7 could be developed as an alternative chemotherapeutic approach against DLBCL and is also effective along with radiotherapy.

Print this article     Email this article
 Next article
 Previous article
 Table of Contents

 Similar in PUBMED
   Search Pubmed for
   Search in Google Scholar for
 Related articles
 Citation Manager
 Access Statistics
 Reader Comments
 Email Alert *
 Add to My List *
 * Requires registration (Free)

 Article Access Statistics
    PDF Downloaded177    
    Comments [Add]    
    Cited by others 1    

Recommend this journal