Peroxiredoxin V Inhibits Emodin-induced Gastric Cancer Cell Apoptosis via the ROS/Bcl2 Pathway

Abstract

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 proapoptotic 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. Gastric cancer (GC) is one of the most common malignancies worldwide; unfortunately, the majority of GC patients is diagnosed at an advanced stage and die within 24 months after surgery because of recurrence and metastasis (1). The cure rate of gastric cancer is extremely low and the risk of treatment is large. It is well known that reactive oxygen species ROS levels are high in cancer cells compared to normal cells. ROS such as hydrogen peroxide, superoxide anions etc. are produced during mitochondria metabolism (2). Low levels of ROS can act as second messengers by participating in a variety of cellular physiological activities such as signal transduction, apoptosis, aging, proliferation and migration of cells. On the contrary, high levels of ROS have been recognized as driving factors in numerous diseases including cancer, aging, neurodegenerative disease, diabetes, cardiovascular disease, stroke, and asthma (3, 4), by inducing lipid, protein and DNA oxidation (5) thereby resulting in increased cellular apoptosis. On the other hand, there are cellular antioxidant mechanisms that clear excessive ROS (6, 7), such as superoxide dismutase (SOD), catalase (Cat), glutathione peroxidase (Gpx) and peroxiredoxin (Prxs). Prx V is a member of the Prxs family, which plays crucial roles in protecting cells from oxidative stress. Prxs are 1183 This article is freely accessible online.

Shikonin-induced Apoptosis of Colon Cancer Cells Is Reduced by Peroxiredoxin V Expression

“…As we showed in our previous study, PrxV is expressed highly in colon cancer cells compared to normal colon tissues. Moreover, the expression level of PrxV is higher in colon cancer cells when compared to the expression of other Prx family members (17). In our data we found PrxV was downregulated by increasing concentrations of Shikonin.…”

“…HCT116, HT29, HT29 Mock, and Prx V-overexpressing HT29 cells (HT29 His-PrxV) cell lines were maintained in Dulbecco's modified Eagle's medium (Invitrogen, Carlsbad, CA, USA) supplemented with 10% fetal bovine serum (FBS; Hyclone, Logan, UT, USA), penicillin (100 U/ml) and streptomycin (100 mg/ml) in an incubator at 37˚C with 5% humidified CO 2 . HCT116 Mock, HCT116 shPrxV and HCT116 His-PrxV cell lines were established as described previously (17).…”

“…Therefore, we examined whether this was related to Shikonin induced colon cancer cell apoptosis. For this purpose, stable HT29 colon cancer cell lines with PrxV overexpression (His- PrxV) and control (HT29 Mock) were established as mentioned in our previous studies (16,17). Expression in cell lines was confirmed by western blotting as shown in Figure 4A.…”

Design, Synthesis, Molecular Docking, and Biological Evaluation of New Emodin Anthraquinone Derivatives as Potential Antitumor Substances

“…[23] In addition, previous reports exhibited that emodin can reverse the apoptosis of gastric cancer cells through addition of ROS scavengers. [24] Therefore, in the present study, the production of intracellular ROS was investigated in HCT116 cells upon treatment with the compound 11c. Figure 4,Aand B depicts that 11c treatment enhanced the number of DCFH-DA positive cells in a dose Interaction Between 11c and BSA Fluorescence spectroscopy, possessing higher accuracy and specificity as compared to UV/VIS spectroscopy, is an important method to study the interaction of biological macromolecules with various organic small molecules, ions and inorganic compounds.…”

The Expression and Prognostic Role of Peroxiredoxins in Lung Cancer

“…Prxs can regulate intracellular signal transduction and cellular metabolism by scavenging intracellular reactive oxygen species [6], and it also regulates cell proliferation, apoptosis and gene expression [7]. Prxs are differentially expressed in various tumors, including pancreatic, liver, colorectal, gastric, and lung cancers [8][9][10][11][12][13].…”