Peroxiredoxin II Regulates Cancer Stem Cells and Stemness-Associated Properties of Cancers

Abstract

Cancer stem cells (CSCs) represent a sub-population of cancer cells with the ability to regulate stemness-associated properties which are specifically responsible for unlimited growth of cancers, generation of diverse cancer cells in differentiated state and resistance to existing chemotherapy and radiotherapy. Even though, current therapies destroy majority of cancer cells, it is believed to leave CSCs without eradicating which may be the conceptualization for chemoresistance and radio-resistance. Reactive oxygen species (ROS) maintain stem cells and regulate the stemness-associated properties of cancers. Beyond the maximum limit, ROS can damage cellular functions of cancers by subjecting them to oxidative stress. Thus, maintenance of ROS level plays an important role in cancers to regulate stemness-associated properties. Peroxiredoxin II (Prx II) is a member of peroxiredoxin antioxidant enzyme family which considers as a regulator of ROS in cellular environments by modulating redox status to maintain CSC phenotype and stemness properties. Prx II has cell type-dependent expression in various types of cancer cells and overexpression or silenced expression of Prx II in cancers is associated with stem cell phenotype and stemness-associated properties via activation or deactivation of various signaling pathways. In this review, we summarized available studies on Prx II expression in cancers and the mechanisms by which Prx II takes parts to regulate CSCs and stemness-associated properties. We further discussed the potential therapeutic effects of altering Prx II expression in cancers for better anticancer strategies by sensitizing cancer cells and stem cells to oxidative stress and inhibiting stemness-associated properties.

The Role of Peroxiredoxin Family in Cancer Signaling

“…Recently, a growing number of studies have found that Prxs regulate their expression and activity, acting as oncogenes that promote carcinogenesis in various cancer types. In addition, Prxs are known to promote the cancer cell stemness [69–71]. Nevertheless, as Prxs have also been shown to suppress tumorigenesis, more studies are required to verify the potential of Prxs as therapeutic targets in each cancer type.…”

Deletion of Peroxiredoxin II Inhibits the Growth of Mouse Primary Mesenchymal Stem Cells Through Induction of the G0/G1 Cell-cycle Arrest and Activation of AKT/GSK3β/β-Catenin Signaling

“…The expression of SRY-related high-mobility-group-box protein-2 and octamer-binding transcription factor-4 was down-regulated in PRDX2-silenced Huh7-H-Ras G12V hepatoma cells, and sphere formation efficiency and epithelial-mesenchymal transition were significantly inhibited (6). Mechanistic studies showed that PRDX2 can regulate stemness of cancer stem cells through a variety of signaling pathways, which contribute to the maintenance of the cancer stem cell properties of hepatocellular carcinoma via VEGF/EGFR/STAT3 signaling and RAS/FOXM1 signaling (33)(34)(35). In the process of isolation and expansion of DMSCs, in vivo 34: 133-141 (2020) we found that knockout of PRDX2 can significantly inhibit the proliferation of stem cells with the increasing cell passage.…”

Metabolic Escape Routes of Cancer Stem Cells and Therapeutic Opportunities

“…The accumulation of ROS causes damage to proteins, lipids and DNA and therefore irrecoverable damage to the cell [27]. Notably, cells have protection mechanisms from oxidative stress, including enzymatic antioxidants such as superoxide dismutase (SOD), catalases, TXN, peroxiredoxins, glutathione (GSH) peroxidases, p38-MAPK and sirtuins [57][58][59] and non-enzymatic molecules such as GSH, vitamin C (ascorbate), vitamin E (tocopherols) and polyphenols [60]. Interestingly, the administration of SOD-1 inhibitor, disulfiram, strongly counteracted breast CSCs expansion by modulating MAPK, NF-kB and STAT3 pathways [61,62].…”