Investigational New Drugs

, Volume 32, Issue 3, pp 424–435 | Cite as

Radiosensitizing activity of a novel Benzoxazine through the promotion of apoptosis and inhibition of DNA repair

  • Suraj Radhamani
  • Christopher BradleyEmail author
  • Terri Meehan-Andrews
  • Saleh K. Ihmaid
  • Jasim Al-Rawi


The DNA dependant protein kinase (DNA-PK) enzyme plays a major part in the repair of double stranded breaks induced by radiation and hence in the radio-resistance of tumour cells. Inhibitors of DNA-PK have been tested successfully in the past for their ability to sensitize cancer cells to the effects of radiation. Here we present a novel benzoxazine, 8-methyl-2-(morpholine-4yl)-7-(pyridine-3-methoxy)-4H-1,3-benzoxacine-4-one (LTU27) and analyse its ability to cause sensitization of lung cancer and colon cancer cells to radiation. There was a significant reduction in survival rate, increase in apoptosis and inhibition in autophosphorylation of DNA-PK and AKT1 after treating them concomitantly with both radiation and LTU27. The mechanism of action appears to be through inhibition of DNA-PK leading to delayed DNA repair and promotion of apoptosis.


Radiosensitizing Colon cancer Lung cancer DNA-PK Benzoxazines 



The authors would like to thank the staff of Peter MacCallum Bendigo Radiotherapy Centre for their support and technical assistance for irradiation of cell lines. We also would like to thank Professor Roger Martin, head of the molecular radiation biology and research division and Andrea Smith, Peter MacCallum cancer centre, Melbourne for their valuable advice and support. Suraj Radhamani was a recipient of Latrobe University Postgraduate Research scholarship (LTUPS) and Full fee Research scholarship (LTUFFRS), with additional research funding by Latrobe University.

Conflict of Interest

The authors declare that they have no conflict of interest.


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Copyright information

© Springer Science+Business Media New York 2014

Authors and Affiliations

  • Suraj Radhamani
    • 1
  • Christopher Bradley
    • 1
    • 2
    Email author
  • Terri Meehan-Andrews
    • 2
  • Saleh K. Ihmaid
    • 1
  • Jasim Al-Rawi
    • 1
  1. 1.School of Pharmacy and Applied Science, La Trobe Institute of Molecular SciencesLa Trobe UniversityBendigoAustralia
  2. 2.La Trobe Rural Health SchoolLa Trobe UniversityBendigoAustralia

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