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Investigational New Drugs

, Volume 29, Issue 4, pp 523–533 | Cite as

A novel structural derivative of natural alkaloid ellipticine, MDPSQ, induces necrosis in leukemic cells

  • M. S. Shahabuddin
  • Mridula Nambiar
  • Balaji T. Moorthy
  • Prakruthi L. Naik
  • Bibha Choudhary
  • Gopal M. Advirao
  • Sathees C. RaghavanEmail author
PRECLINICAL STUDIES

Summary

DNA intercalating molecules are promising chemotherapeutic agents. In the present study, a novel DNA intercalating compound of pyrimido[4′,5′:4,5]selenolo(2,3-b)quinoline series having 8-methyl-4-(3 diethylaminopropylamino) side chain is studied for its chemotherapeutic properties. Our results showed that 8-methyl-4-(3 diethylaminopropylamino) pyrimido [4′,5′:4,5] selenolo(2,3-b)quinoline (MDPSQ) induces cytotoxicity in a time- and concentration-dependent manner on leukemic cell lines. Both cell cycle analysis and tritiated thymidine assays revealed that MDPSQ affects DNA replication. Treatment with MDPSQ resulted in both elevated levels of DNA strand breaks and repair proteins, further indicating its cytotoxic effects. Besides, Annexin V/PI staining revealed that MDPSQ induces cell death by triggering necrosis rather than apoptosis.

Keywords

Chemotherapy Double-strand breaks Cytotoxicity DNA damage Anti cancer drugs 

Notes

Acknowledgements

We thank Dr. Kavitha C.V., Ms. Nishana M. and members of SCR laboratory for critical reading of the manuscript. This work was supported by Lady Tata Memorial Trust international award for leukemia research (London) for SCR. SMS is supported by DBT postdoctoral fellowship from India. MN is supported by Senior Research Fellowship from CSIR, India.

Supplementary material

10637_2009_9379_MOESM1_ESM.ppt (283 kb)
Suppl. Figure 1 Quantification of cell cycle analysis of K562 and CEM cells following treatment with MDPSQ. K562 (A,B) and CEM (D,E) cells were treated with MDPSQ as described in Fig. 3. Quantification of different cell cycle phases is shown. C. Western blot showing expression of PCNA. The α-Tubulin was used as an internal loading control (PPT 283 kb)

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Copyright information

© Springer Science+Business Media, LLC 2010

Authors and Affiliations

  • M. S. Shahabuddin
    • 1
  • Mridula Nambiar
    • 1
  • Balaji T. Moorthy
    • 1
  • Prakruthi L. Naik
    • 2
  • Bibha Choudhary
    • 1
  • Gopal M. Advirao
    • 2
  • Sathees C. Raghavan
    • 1
    Email author
  1. 1.Department of BiochemistryIndian Institute of ScienceBangaloreIndia
  2. 2.Department of BiochemistryKuvempu UniversityDavanagereIndia

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