Modulation of therapy-induced senescence by reactive lipid aldehydes

摘要: Current understanding points to unrepairable chromosomal damage as the critical determinant of accelerated senescence in cancer cells treated with radiation or chemotherapy. Nonetheless, potent inducer etoposide not only targets topoisomerase II induce DNA but also produces abundant free radicals, increasing cellular reactive oxygen species (ROS). Toward examining roles for and oxidative stress therapy-induced senescence, we developed a quantitative flow cytometric assay screened 36 redox-active agents enhancers an otherwise ineffective dose radiation. While failed correlate total ROS, enhancers, other effective inhibitors each produced high levels lipid peroxidation. The aldehyde 4-hydroxy-2-nonenal, peroxidation end product, was sufficient irradiated cells. In turn, sequestering aldehydes hydralazine blocked effects inducers. These results suggest that potentiates from chemotherapy drive senescence.