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. 2013 Dec;9(4):350-357.
doi: 10.1007/s11888-013-0190-5.

REACTIVE OXYGEN SPECIES AND COLORECTAL CANCER

Sandeep Sreevalsan  1 , Stephen Safe  2
Affiliations

REACTIVE OXYGEN SPECIES AND COLORECTAL CANCER

Sandeep Sreevalsan et al. Curr Colorectal Cancer Rep. 2013 Dec.

Abstract

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 pro-oncogenic Spregulated genes important for cancer cell proliferation, survival and metastasis. The mechanism of these responses involve ROS-dependent downregulation of microRNA-27a (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 development of drug combinations for cancer chemotherapy.

Keywords: Colon cancer; antioxidants; mechanism based drugs; microRNA; reactive oxygen Species; specificity transcription factors; targeted therapy; zinc finger DNA binding proteins.

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Figures

Figure 1
Figure 1. ROS dependent downregulation of Sp proteins and other oncogenic factors
Treatment of colon cancer cells with ROS inducing drugs disrupt miR-ZBTB interaction to induce Sp repressors ZBTB10 and or ZBTB4 that act as transcriptional repressors on GC-rich cis elements [41, 42].
See this image and copyright information in PMC

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