Reactive Oxygen Species and Colorectal Cancer

Several agents used for treatment of colon and other cancers induce reactive oxygen species (ROS), and this plays an important role in their anticancer activities. In addition to the well-known proapoptotic effects of ROS inducers, these compounds also decrease expression of specificity protein (Sp) transcription factors Sp1, Sp3, and Sp4 and several prooncogenic Sp-regulated genes important for cancer cell proliferation, survival, and metastasis. The mechanism of these responses involves ROS-dependent downregulation of miR-27a or miR-20a (and paralogs) and induction of two Sp repressors, ZBTB10 and ZBTB4, respectively. This pathway significantly contributes to the anticancer activity of ROS inducers and should be considered in the development of drug combinations for cancer chemotherapy.