Abstract

Cancer stem cells (CSCs) are a key target for reducing tumor growth, metastasis, and recurrence. Redox status is a critical factor in the maintenance of CSCs, and the antioxidant enzyme Peroxiredoxin 2 (Prdx2) plays an important role in the development of colon cancer. Therefore, we investigated the contribution of Prdx2 to the maintenance of stemness of colon CSCs. Here, we used short-hairpin RNAs and a Prdx2-overexpression vector to determine the effects of Prdx2. We demonstrated that knockdown of Prdx2 reduced the self-renewal and sphere formation and resulted in increased 5-FU-induced apoptosis in human colon CSCs. Prdx2 overexpression induced reversion of the self-renewal and sphere formation. Furthermore, the effects of Prdx2 resulted in an altered expression of stemness associated with the Hh/Gli1 signaling pathway. Finally, knockdown of Prdx2 in CD133+ cells reduced the volume of xenograft tumors in BALB/c-nu mice. Taken together, colon CSCs overexpress Prdx2, which promotes their stem cell properties via the Hh/Gli1 signaling pathway. The results suggest that Prdx2 may be an effective therapeutic target for the elimination of CSCs in colorectal cancer.

Highlights

  • Colorectal cancer is the fifth most common cancer and remains one of the leading causes of cancer-related deaths in China [1], emphasizing the need for a better understanding of the biology of colorectal cancer and for the development of new therapeutic strategies based on that biology

  • Our current study shows that the protein level of Peroxiredoxin 2 (Prdx2) is markedly increased in CD133+ colon cancer cells compared with CD133- cells

  • These data shows that Prdx2 is overexpressed in cancer stem cells (CSCs) from colon cancer compared with non-CSCs, which indicates Prdx2 may play an important role in CSCcorrelated properties

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Summary

Introduction

Colorectal cancer is the fifth most common cancer and remains one of the leading causes of cancer-related deaths in China [1], emphasizing the need for a better understanding of the biology of colorectal cancer and for the development of new therapeutic strategies based on that biology. Several recent studies have reported that reactive oxygen species (ROS) are associated with the stemness of CSCs. Diehn et al reported that low levels of ROS may be conducive to the maintenance of CSCs and to their resistance to ionizing radiation [3]. Ye et al reported that lung cancer stem cells (LCSCs) contained lower intracellular concentrations of ROS relative to nonLCSCs and that ROS generation increased during the differentiation of LCSCs [5]. These studies indicate that redox status plays an important role in CSC maintenance

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