期刊名称：Journal of Radiation Research and Applied Sciences
印刷版ISSN：1687-8507
出版年度：2017
卷号：10
期号：3
页码：204-213
DOI：10.1016/j.jrras.2017.04.008
出版社：Elsevier B.V.
摘要：Abstract 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 two novel benzoxazines (LTU28 and LTU31) and analyse their ability to cause sensitization of 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 with {LTU28} concomitantly with radiation. The mechanism of action by {LTU28} appears to be through inhibition of DNA-PK leading to delayed {DNA} repair and promotion of apoptosis. {LTU31} showed an inhibition in the phosphorylation of BRCA1, thereby blocking {DNA} repair by homologous recombination.
