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Apoptosis of pancreatic β‑cells is involved in the pathogenesis of type I and II diabetes. Peroxiredoxin I (Prx I) serves an important role in regulating cellular apoptosis; however, the role of Prx I in pancreatic β‑cell apoptosis is not completely understood. In the present study, the role of peroxiredoxin 1 (Prx I) during streptozotocin (STZ)‑induced apoptosis of pancreatic β‑cells was investigated. The expression level of Prx I was decreased by STZ treatment in a time‑dependent manner, and apoptosis of Prx I knockdown MIN6 cells was increased by STZ stimulation, compared with untransduced MIN6 cells. Furthermore, an intraperitoneal injection of STZ increased pancreatic islet damage in Prx I knockout mice, compared with wild‑type and Prx II knockout mice. AKT and glycogen synthase kinase (GSK)‑3β phosphorylation significantly decreased following Prx I knockdown in MIN6 cells. However, phosphorylated β‑catenin and p65 levels significantly increased after STZ stimulation, compared with untransduced cells. The results of the present study indicate that deletion of Prx I mediated STZ‑induced pancreatic β‑cell death in vivo and in vitro by regulating the AKT/GSK‑3β/β‑catenin signaling pathway, as well as NF‑κB signaling. These findings provide a theoretical basis for treatment of pancreatic damage.

Background: Peroxiredoxin II (PRDX2) performs unique roles in cells. It can reduce peroxides through cysteine residues, and helps prevent the effects of oxidative stress on cells. It is closely related to the occurrence and development of various diseases, especially alcoholic liver injury and even liver cancer. The metabolism of alcohol in hepatocytes leads to the increase in the levels of reactive oxygen species (ROS), oxidative stress, injury, and apoptosis. Therefore, this study focused on the investigating the protection conferred by PRDX2 against alcohol-induced apoptosis of hepatocytes., Materials and Methods: PRDX2 inhibition of alcohol-induced apoptosis in L02 hepatocytes was analyzed by 3-(4,5-dimethylthiazol-2-yl)-2,5-diphenyltetrazolium bromide assay, fluorescence microscopy, flow cytometry, western blotting and hematoxylin and eosin staining., Results: The results showed that the levels of reactive oxygen species, protein kinase B, β-catenin, B-cell lymphoma-2 (BCL2), BCL-XL, BCL2-associated X, cleaved caspase-3, and cleaved poly (ADP-ribose) polymerase in PRDX2-silenced cells were increased significantly after the treatment of cells with ethanol. Similar results were obtained in an in vivo Prdx2-knockout mouse model of alcoholic liver injury. Therefore, PRDX2 may regulate the phosphorylation of the AKT signal protein by eliminating reactive oxygen species from cells, and it inhibits the downstream mitochondria-dependent apoptosis pathway, and, thereby, the apoptosis of cells., Conclusion: Thus, PRDX2 may be a potential molecular target for the prevention and treatment of alcoholic liver injury., (Copyright© 2020, International Institute of Anticancer Research (Dr. George J. Delinasios), All rights reserved.)

Backgorund/Aim: Wogonin, a flavonoid-like compound extracted from the root of Scutellaria baicalensis Georgi, has been shown to have anticancer effects against cancer cells. Osteosarcoma is the most malignant type of bone cancer and can appear in any bone, with a high propensity for relapse and metastasis. The present study aimed to assess the anticancer effects of wogonin on osteosarcoma stem cells., Materials and Methods: The cytotoxic effects of wogonin on CD133 + Cal72 osteosarcoma stem cells were assessed through in vitro experiments by MTT assay, transwell assay, sphere-formation assay, flow cytometry, immunocytochemistry and western blotting., Results: Wogonin suppressed stem cell characteristics and the expression of stem cell-related genes by regulating reactive oxygen species (ROS) levels and ROS-related signaling of CD133 + Cal72 cells, effects which were reversed by ROS scavenger N-acetylcysteine., Conclusion: Wogonin may be a promising candidate for successful clinical management of osteosarcoma by regulating ROS-related mechanisms and stem cell-related genes., (Copyright© 2020, International Institute of Anticancer Research (Dr. George J. Delinasios), All rights reserved.)

Background/aim: Numerous studies on various cancer cell lines have reported that direct exposure to non-thermal plasma treatment using plasma-activated medium (PAM) can be applied as a novel technology for cancer therapy. In this study, we investigated the inhibitory effects of PAM on Aspc1 pancreatic cancer cells and the mechanisms responsible for the cell death observed., Materials and Methods: A colony-formation, sphere-formation, wound-healing and transwell assays, immunocytochemistry and western blot analysis were used monitor effects of PAM., Results: PAM induced a greater cytotoxic effect in pancreatic cancer cells compared to that induced in NIH3T3 cells and 293T cells, and significantly inhibited colony and sphere formation, and cell migration of Aspc1 cells. Furthermore, PAM treatment increased the accumulation of reactive oxygen species (ROS) and reduced the mitochondrial membrane potential in Aspc1 cells. In addition, PAM treatment down-regulated the AKT serine/threonine kinase 1/signal transducer and activator of transcription 3 signaling pathway and induced ROS-dependent cellular autophagy., Conclusion: Our findings suggest that PAM can induce apoptosis of Aspc1 cells through ROS-dependent autophagy and may be a candidate for use in pancreatic cancer therapeutics., (Copyright© 2020, International Institute of Anticancer Research (Dr. George J. Delinasios), All rights reserved.)

Background/aim: Dermal mesenchymal stem cells (DMSCs) are pluripotent stem cells found in the skin which maintain the thickness of the dermal layer and participate in skin wound healing., Materials and Methods: The MTT assay was performed to detect cell proliferation and cell-cycle progression and cell-surface markers were assessed by flow cytometry. The levels of proteins in related signaling pathways were detected by western blotting assay and the translocation of β-catenin into the nucleus were detected by immunofluorescence. Red oil O staining was performed to examine the differentiational ability of DMSCs., Results: Knockout of PRDX2 inhibited DMSC cell growth, and cell-cycle arrest at G 0 /G 1 phase; p16, p21 and cyclin D1 expression levels in Prdx2 knockout DMSCs were significantly increased. Furthermore, AKT phosphorylation were significantly increased in Prdx2 knockout DMSCs, GSK3β activity were inhibited, result in β-Catenin accumulated in the nucleus., Conclusion: In conclusion, these results demonstrated that PRDX2 plays a pivotal role in regulating the proliferation of DMSCs, and this is closely related to the AKT/glycogen synthase kinase 3 beta/β-catenin signaling pathway., (Copyright© 2020, International Institute of Anticancer Research (Dr. George J. Delinasios), All rights reserved.)

Background/aim: Peroxiredoxin (Prx) protein family is aberrantly expressed in various cancers including gastric cancer. Among the six family members, Prx V has been known as an antioxidant enzyme which scavenges intracellular reactive oxygen species (ROS) and modulates cellular apoptosis. This study aimed at investigating the role of Prx V in apoptosis of gastric cancer cells., Materials and Methods: Stably constructed Prx V knockdown, over-expression and mock AGS cells (a human gastric adenocarcinoma cell line) were used to study the effect of Prx V on emodin-induced apoptosis by western blotting, cell viability, apoptosis and ROS detection assays., Results: Overexpression of Prx V significantly decreased emodin-induced cellular apoptosis and ROS levels compared to Mock and Prx V knockdown AGS cells. Also, overexpression of Prx V down-regulated the expression of pro-apoptotic proteins, Bad and cleaved PARP, and increased the expression of anti-apoptotic protein, Bcl2., Conclusion: Prx V suppresses AGS cell apoptosis via scavenging intracellular ROS and modulating apoptosis-related markers., (Copyright© 2019, International Institute of Anticancer Research (Dr. George J. Delinasios), All rights reserved.)

Quinalizarin may be a potential chemical agent for cancer therapy, as it exerts anti‑tumour effects against a variety of different types of cancer. However, the underlying regulatory mechanism and signalling pathways of quinalizarin in lung cancer cells remains unknown. The present study sought to investigate the effects of quinalizarin on proliferation, apoptosis and reactive oxygen species (ROS) generation in lung cancer. MTT assays were used to evaluate the effects of quinalizarin on the viability of lung cancer A549, NCI‑H460 and NCI‑H23 cells. Flow cytometry was employed to evaluate the effects of quinalizarin on the cell cycle, apoptosis and ROS generation in A549 cells. Western blotting was performed to detect cell cycle and apoptosis‑associated protein expression levels in A549 cells. Quinalizarin inhibited A549, NCI‑H460 and NCI‑H23 cell proliferation and induced A549 cell cycle arrest at the G0/G1 phase. Quinalizarin induced apoptosis by upregulating the expression of B‑cell lymphoma 2 (Bcl‑2)‑associated agonist of cell death, cleaved‑caspase‑3 and cleaved‑poly (adenosine diphosphate‑ribose) polymerase, and downregulating the expression of Bcl‑2. Furthermore, quinalizarin activated mitogen‑activated protein kinase (MAPK) and p53, and inhibited the protein kinase B and signal transducer and activator of transcription‑3 (STAT3) signalling pathways. In addition, quinalizarin increased ROS generation. The ROS scavenger N‑acetyl‑L‑cysteine restored quinalizarin‑induced cell apoptosis, and inactivated the MAPK and STAT3 signalling pathways. The results of the present study demonstrated that quinalizarin induces G0/G1 phase cell cycle arrest and apoptosis via ROS mediated‑MAPK and STAT3 signalling pathways.

The importance of microglial reactive oxygen species (ROS) signaling in neuroinflammatory processes has been well demonstrated; however, relatively little is known regarding the related mechanisms underlying these processes. Here, we show that ROS-dependent signal pathways that govern microglial phagocytosis are highly dependent upon nicotinamide adenine dinucleotide phosphate (NADPH) oxidase (Nox) activation. Specifically, phagocytosis was greatly reduced by both antioxidant and Nox inhibitor treatments in lipopolysaccharide (LPS)-stimulated BV-2 microglia. Additionally, there was a marked reduction in intracellular ROS content. These results suggest that Nox is the main ROS source for LPS-induced microglial phagocytosis. More decisive evidence for the involvement of ROS in phagocytosis was obtained from an examination of phosphatidyl inositol 3-kinase (PI3-K) and p38 mitogen-activated protein kinase (MAPK) signal pathway activation under reduced ROS levels. These two kinases were activated by LPS treatment and inhibited by ROS neutralization and Nox inhibition. We conclude that microglial phagocytosis requires ROS-dependent PI3-K and p38 MAPK activation and that Nox-derived ROS functions as an upstream regulator of both PI3-K and p38 MAPK. These findings will provide a fundamental basis for a therapeutic modality in inflammation-mediated neurodiseases.