Mechanisms of Hydroxyurea-Induced Cellular Senescence: An Oxidative Stress Connection?

Figure 1

Main mechanisms of hydroxyurea cytotoxicity. HU functions as a radiation sensitizer by synchronizing cancer cells in the radiation-sensitive cell G1-S cycle interphase and inhibition of the DNA damage repair response. Also, HU sensitizes cancer cells to chemotherapy by promoting loss of extrachromosomal amplified gene elimination, metaphase chromosome, and DNA breaks damage. Moreover, HU inhibits the ribonucleotide reductase (RNR) that results in a drastic reduction of the deoxyribonucleotide pool necessary for DNA synthesis. Depletion of dNTPs promotes DNA replication fork collapse, strand break, and oxidative stress. For more details, see the text.