Silencing Prx1 and/or Prx5 sensitizes human esophageal cancer cells to ionizing radiation and increases apoptosis via intracellular ROS accumulation

Abstract

Aim: To investigate whether down-regulation of peroxiredoxin 1 (Prx1) and/or peroxiredoxin 5 (Prx5) sensitizes human esophageal cancer cells to ionizing radiation (IR). Methods: Human esophageal carcinoma cell lines Eca-109 and TE-1 were used. Prx mRNA expression profiles in Eca-109 and TE-1 cells were determined using RT-PCR. Two highly expressed isoforms of Prxs, Prx1 and Prx5, were silenced by RNA interference (RNAi). Following IR, intracellular reactive oxygen species (ROS) and apoptosis were measured using flow cytometry, the activities of catalase, superoxide dismutase and glutathione peroxidase were measured, and the radiosensitizing effect of RNAi was observed. Tumor xenograft model was also used to examine the radiosensitizing effect of RNAi in vivo. Results: Down-regulation of Prx1 and/or Prx5 by RNAi does not alter the activities of catalase, superoxide dismutase and glutathione peroxidase, but made human tumor cells more sensitive to IR-induced apoptosis both in vitro and in vivo. When the two isoforms were decreased simultaneously, intracellular ROS and apoptosis significantly increased after IR. Conclusion: Silencing Prx1 and/or Prx5 by RNAi sensitizes human Eca-109 and TE-1 cells to IR, and the intracellular ROS accumulation may contribute to the radiosensitizing effect of the RNAi.

Disturbance of redox status enhances radiosensitivity of hepatocellular carcinoma

“…However, excess ROS can be deleterious to cellular molecules, including proteins, membrane lipids, and DNA, which could lead to DNA fragmentation and lipid peroxidation [36], resulting in cellular death through necrosis or apoptosis. X-ray, γ-radiation, and other ionizing radiations can promote ROS formation in cells by water ionization, which could result in apoptosis in tumors [37,38]. Thus, increased production of ROS is an important mechanism during radiotherapy.…”

Peroxiredoxin 1 – an antioxidant enzyme in cancer

“…Interestingly, silencing PRDX1 leads to increased levels of tumour suppressor genes LKB1 and p‐AMPK, and decreases the oncogene Aurora A expression, suggesting that PRDX1 may affect carcinogenesis 64. Apart from these, PRDX1 also has a protective function in dioscin/ionizing radiation‐induced ROS accumulation in oesophageal cancer cells 66, 67. These data highlight that PRDX1 promotes tumourigenesis by functioning as “accomplices” of certain oncoproteins or by the activity of its antioxidant enzyme.…”

SOD Therapeutics: Latest Insights into Their Structure-Activity Relationships and Impact on the Cellular Redox-Based Signaling Pathways

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“…12) (8,35,93,142,177,191,233,235,245). In a cell culture, the MnP/ascorbate showed promise as potential treatment of inflammatory breast cancer; the noncaspase-, but AIF-and NF-jB-based apoptosis was promoted (82).…”