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Propyl gallate (PG) has been found to exert an inhibitory effect on the growth of different cell types, including lung cancer cells. However, little is known about the cytotoxicological effects of PG specifically on normal primary lung cells. The current study examined the cellular effects and cell death resulting from PG treatment in human pulmonary fibroblast (HPF) cells. DNA flow cytometry results demonstrated that PG (100-1,600 µM) had a significant impact on the cell cycle, leading to G1 phase arrest. Notably, 1,600 µM PG slightly increased the number of sub-G1 cells. Additionally, PG (400-1,600 µM) resulted in the initiation of cell death, a process that coincided with a loss of mitochondrial membrane potential (MMP; ΔΨm). This loss of MMP (ΔΨm) was evaluated using a FACS cytometer. In PG-treated HPF cells, inhibitors targeting pan-caspase, caspase-3, caspase-8, and caspase-9 showed no significant impact on the quantity of annexin V-positive and MMP (ΔΨm) loss cells. The administration of siRNA targeting Bax or caspase-3 demonstrated a significant attenuation of PG-induced cell death in HPF cells. However, the use of siRNAs targeting p53, Bcl-2, or caspase-8 did not exhibit any notable effect on cell death. Furthermore, none of the tested MAPK inhibitors, including MEK, c-Jun N-terminal kinase (JNK), and p38, showed any impact on PG-induced cell death or the loss of MMP (ΔΨm) in HPF cells. In conclusion, PG induces G1 phase arrest of the cell cycle and cell death in HPF cells through apoptosis and/or necrosis. The observed HPF cell death is mediated by the modulation of Bax and caspase-3. These findings offer insights into the cytotoxic and molecular effects of PG on normal HPF cells. [ABSTRACT FROM AUTHOR]

With the advent of the big data era, security issues in the context of artificial intelligence (AI) and data analysis are attracting research attention. In the metaverse, which will become a virtual asset in the future, users' communication, movement with characters, text elements, etc., are required to integrate the real and virtual. However, they can be exposed to threats. Particularly, various hacker threats exist. For example, users' assets are exposed through notices and mail alerts regularly sent to users by operators. In the future, hacker threats will increase mainly due to naturally anonymous texts. Therefore, it is necessary to use the natural language processing technology of artificial intelligence, especially term frequency-inverse document frequency, word2vec, gated recurrent unit, recurrent neural network, and long-short term memory. Additionally, several application versions are used. Currently, research on tasks and performance for algorithm application is underway. We propose a grouping algorithm that focuses on securing various bridgehead strategies to secure topics for security and safety within the metaverse. The algorithm comprises three modules: extracting topics from attacks, managing dimensions, and performing grouping. Consequently, we create 24 topic-based models. Assuming normal and spam mail attacks to verify our algorithm, the accuracy of the previous application version was increased by ~0.4%-1.5%. [ABSTRACT FROM AUTHOR]

Propyl gallate (3,4,5-trihydroxybenzoic acid propyl ester, PG) has an anti-proliferative effect in various cells. In this study, Calu-6 and A549 lung cancer cells were used to examine the anti-proliferative effect of PG in relation to reactive oxygen species (ROS) and glutathione (GSH) levels. PG (100-1,600 μM) dose-dependently inhibited the proliferation of Calu-6 and A549 cells at 24 h, and PG at 800-1,600 μM strongly induced cell death in both cell lines. PG (800-1,600 μM) increased cellular metabolism in Calu-6 but not A549 cells at 4 h. PG either increased or decreased ROS levels, including O2˙- and ˙OH, depending on the incubation doses and times of 1 or 24 h. Even these effects differed between Calu-6 and A549 cell types. PG reduced the activity of superoxide dismutase (SOD) in Calu-6 cells, and it augmented the activity of catalase in A549 cells. PG dose-dependently increased the number of GSH depleted cells in both Calu-6 and A549 cells at 24 h. In addition, PG decreased GSH levels in both lung cancer cells at 1 h. Furthermore, diethyldithiocarbamate (DDC; an inhibitor of SOD) and 3-amino-1,2,4-triazole (AT; an inhibitor of catalase) differently affected cellular metabolism, ROS and GSH levels in PG-treated and PG-untreated Calu-6 and A549 cells at 1 h. In conclusion, PG dose-dependently decreased the proliferation of Calu-6 and A549 lung cancer cells, which was related to changes in ROS levels and the depletion of GSH. [ABSTRACT FROM AUTHOR]

Gallic acid (GA) exhibits a number of cellular effects, including apoptosis, which is associated with oxidative stress. The present study investigated the effects of GA on calf pulmonary arterial endothelial cell (CPAEC) growth and death, along with the levels of reactive oxygen species (ROS) and glutathione (GSH). GA treatment inhibited the growth of CPAECs at 24 h, and the half‑maximal inhibitory concentration (IC50) value of GA was ~30 μM. GA treatment also induced cell death, which was accompanied by a loss of mitochondrial membrane potential (ΔѰm). GA treatment in CPAECs resulted in decreased ROS levels, including O2 •‑, whereas the number of GSH‑depleted cells increased. Neither a pan‑caspase inhibitor (benzyloxycarbonyl‑Val‑Ala‑Asp‑fluoromethylketone) nor buthionine sulfoximine treatment affected GA‑induced cell growth inhibition, cell death, ROS and GSH levels in CPAECs, whereas co‑treatment with N‑acetyl‑cysteine (NAC) resulted in enhanced cell growth inhibition, cell death and ΔѰm loss in these cells. Although NAC treatment did not significantly influence ROS levels in GA‑treated CPAECs, it significantly enhanced GSH depletion in these cells. In conclusion, GA inhibited the growth of CPAECs via cell death, which was associated with GSH depletion rather than alterations to ROS levels. [ABSTRACT FROM AUTHOR]

Oxidative stress induces apoptosis in endothelial cells (ECs). Reactive oxygen species (ROS) promote cell death by regulating the activity of various mitogen-activated protein kinases (MAPKs) in ECs. The present study investigated the effects of MAPK inhibitors on cell survival and glutathione (GSH) levels upon H2O2 treatment in calf pulmonary artery ECs (CPAECs). H2O2 treatment inhibited the growth and induced the death of CPAECs, as well as causing GSH depletion and the loss of mitochondrial membrane potential (MMP). While treatment with the MEK or JNK inhibitor impaired the growth of H2O2-treated CPAECs, treatment with the p38 inhibitor attenuated this inhibition of growth. Additionally, JNK inhibitor treatment increased the proportion of sub-G1 phase cells in H2O2-treated CPAECs and further decreased the MMP. However, treatment with a p38 inhibitor reversed the effects of H2O2 treatment on cell growth and the MMP. Similarly, JNK inhibitor treatment further increased, whereas p38 inhibitor treatment decreased, the proportion of GSH-depleted cells in H2O2-treated CPAECs. Each of the MAPK inhibitors affected cell survival, and ROS or GSH levels differently in H2O2-untreated, control CPAECs. The data suggest that the exposure of CPAECs to H2O2 caused the cell growth inhibition and cell death through GSH depletion. Furthermore, JNK inhibitor treatment further enhanced, whereas p38 inhibitors attenuated, these effects. Thus, the results of the present study suggest a specific protective role for the p38 inhibitor, and not the JNK inhibitor, against H2O2-induced cell growth inhibition and cell death. [ABSTRACT FROM AUTHOR]

Pyrogallol (PG) induces apoptosis in lung cancer cells via the overproduction of O2•‑ and affects mitogen‑activated protein kinases (MAPKs) in these cells. The aim of the present study was to elucidate the effect of PG and/or MAPK inhibitors on human pulmonary fibroblast (HPF) cell viability in relation to reactive oxygen species (ROS) and glutathione (GSH). Treatment with 50 or 100 µM PG inhibited the viability of HPF cells, and induced cell death and the loss of mitochondrial membrane potential (MMP; ΔΨm). In particular, treatment with 100 µM PG induced cell death via apoptosis as well as necrosis in HPF cells. PG increased mitochondrial O2•‑ levels and the number of GSH‑depleted HPF cells. All the MAPK (mitogen‑activated protein kinase kinase, c‑Jun N‑terminal kinase and p38) inhibitors enhanced the inhibition of cell viability, cell death and MMP (ΔΨm) loss in 100 µM PG‑treated HPF cells. All the inhibitors increased the O2•‑ levels in 100 µM PG‑treated HPF cells, but none of the inhibitors significantly altered the PG‑induced GSH depletion. In conclusion, PG treatment induced cell death via apoptosis and necrosis in HPF cells. Treatment with MAPK inhibitors slightly enhanced cell death in PG‑treated HPF cells. HPF cell death induced by PG and/or MAPK inhibitors was at least partially associated with changes in O2•‑ levels and GSH content. The present data provided useful information to understand PG‑induced normal lung cell death in association with MAPK signaling pathways and ROS levels. [ABSTRACT FROM AUTHOR]

Reactive oxygen species (ROS) are associated with various pathophysiological processes of vascular smooth muscle cells (VSMCs). Pyrogallol (PG) induces the superoxide anion (O2•-)-mediated cell death of numerous cell types. The present study aimed to investigate the effects of exogenous hydrogen peroxide (H2O2) and PG treatment on the cell growth and death of human pulmonary artery smooth muscle cells (HPASMCs), with regards to intracellular ROS and glutathione (GSH) levels, as determined by MTT and cell number assays. H2O2 led to reduced growth of HPASMCs, with a half maximal inhibitory concentration of 250-500 μM at 24 h, and induced apoptosis, as determined by Annexin V-staining and benzyloxycarbonyl-Val-Ala-Asp-fluoromethylketone treatment. However, PG did not strongly induce growth inhibition and death of HPASMCs. In addition, H2O2 led to increased ROS levels, including mitochondrial O2•-, and induced GSH depletion in HPASMCs. Treatment with N-acetyl cysteine (NAC) attenuated apoptotic cell death and ROS levels in H2O2-treated HPASMCs, and also prevented GSH depletion. Notably, PG treatment did not increase ROS levels, including mitochondrial O2•-. Furthermore, NAC induced a significant increase in mitochondrial O2•- levels in PG-treated HPASMCs, and cell death and GSH depletion were significantly increased. L-buthionine sulfoximine intensified cell death and GSH depletion in PG-treated HPASMCs. In conclusion, exogenous H2O2 induced growth inhibition and cell death of HPASMCs via GSH depletion. [ABSTRACT FROM AUTHOR]

Auranofin (Au), an inhibitor of thioredoxin reductase, is a known anti-cancer drug. In the present study, the anti-growth effect of Au on HeLa cervical cancer cells was examined in association with levels of reactive oxygen species (ROS) and glutathione (GSH). Au inhibited the growth of HeLa cells with an IC50 of ~2 µM at 24 h. This agent induced apoptosis and necrosis, accompanied by the cleavage of poly (ADP-ribose) polymerase and loss of mitochondrial membrane potential. The pan-caspase inhibitor, benzyloxycarbonyl-Val-Ala-Asp-fluoromethylketone, prevented apoptotic cell death and each of the assessed caspase inhibitors inhibited necrotic cell death induced by Au. With respect to the levels of ROS and GSH, Au increased intracellular O2 ... in the HeLa cells and induced GSH depletion. The pan-caspase inhibitor reduced the levels of O2 ... and GSH depletion in Au-treated HeLa cells. The antioxidant, N-acetyl cysteine, not only attenuated apoptosis and necrosis in the Au-treated HeLa cells, but also decreased the levels of O2 ... and GSH depletion in the cells. By contrast, L-buthionine sulfoximine, a GSH synthesis inhibitor, intensified cell death O2 ... and GSH depletion in the Au-treated HeLa cells. In conclusion, Au induced apoptosis and necrosis in HeLa cells via the induction of oxidative stress and the depletion of GSH. [ABSTRACT FROM AUTHOR]

PX-12, as an inhibitor of thioredoxin (Trx), has antitumor activity. However, little is known about the toxicological effect of PX-12 on cervical cancer cells. In the present study, the growth inhibitory effects of PX-12 on HeLa cervical cancer cells in association with reactive oxygen species (ROS) and glutathione (GSH) levels were investigated. Based on MTT assays, PX-12 inhibited the growth of HeLa cells with an IC50 value of ~7 µM at 72 h. DNA low cytometry analysis indicated that 5 and 10 µM PX-12 signiicantly induced a G2/M phase arrest of the cell cycle. PX-12 also increased the number of dead cells and annexin V-fluorescein isothiocyanate-positive cells, which was accompanied by the loss of mitochondrial membrane potential. All the investigated caspase inhibitors signiicantly rescued certain cells from PX-12-induced HeLa cell death. With respect to ROS and GSH levels, PX-12 increased ROS levels (including O2•-) in HeLa cells and induced GSH depletion. N-acetyl cysteine markedly reduced the levels of 2•- in PX-12-treated HeLa cells, and prevented apoptotic cell death and GSH depletion in these cells. By contrast, L-buthionine sulfoximine intensiied cell death and GSH depletion in PX-12-treated HeLa cells. To conclude, this is the irst study to demonstrate that PX-12 inhibits the growth of HeLa cells via G2/M phase arrest, as well as inhibiting apoptosis; the effect was associated with intracellular increases in ROS levels and GSH depletion. [ABSTRACT FROM AUTHOR]

Gallic acid (GA) has various biological properties including anti-cancer effect. However, little is known about the toxicological effect of GA in primary normal cells. Here, we evaluated the effects of GA on human pulmonary fibroblast (HPF) cells in relation to reactive oxygen species (ROS) and glutathione (GSH). GA inhibited the growth of HPF cells at 24 hours in a dose-dependent manner. GA also induced HPF cell death, which was accompanied by the loss of mitochondrial membrane potential (MMP; ΔΨm). GA increased ROS levels including O2•- and GSH-depleted cell numbers in HPF cells at 24 hours. Treatment with 2 mM N-acetyl-cysteine (NAC) intensified growth inhibition and death in GA-treated HPF cells. NAC decreased ROS levels and increased GSH depletion in these cells. Treatment with 10 μM L-buthionine sulfoximine (BSO) also enhanced growth inhibition and death in GA-treated HPF cells. BSO increased ROS levels and GSH depletion in these cells. In conclusion, GA-induced HPF cell death was accompanied by ROS increase and GSH depletion. The changes of ROS and GSH levels by NAC and BSO appeared to affect cell growth and death in GA-treated HPF cells. [ABSTRACT FROM PUBLISHER]

Propyl gallate (PG) as a synthetic antioxidant exerts a variety of effects on tissue and cell functions. Here, we investigated the effects of MAPK (MEK, JNK and p38) inhibitors on PG-treated HeLa cells in relation to cell death, ROS and GSH levels. PG induced cell growth inhibition and apoptosis in HeLa cells, which was accompanied by the loss of mitochondrial membrane potential (MMP; ΔΨ). ROS levels were increased or decreased in PG-treated HeLa cells depending on the incubation times. PG also increased GSH depleted cell numbers in HeLa cells. All the MAPK inhibitors slightly enhanced cell growth inhibition, death and MMP (ΔΨ) loss, and increased ROS levels in PG-treated HeLa cells. However, MAPK inhibitors did not significantly affect GSH depletion in PG-treated cells. In conclusion, the enhanced effect of MAPK inhibitors on PG-induced HeLa cell death was accompanied by increasing ROS levels but the effect was not related to changes of GSH level. [ABSTRACT FROM AUTHOR]

Butylated hydroxyanisole (BHA), a synthetic antioxidant is commonly used as a preservative in food and pharmaceutical agents. Despite the assumed low toxicity of BHA, it exerts a variety of effects on tissues and cell functions. In this study, the authors investigated the effects of BHA on the growth inhibition and death of HeLa cervical cancer cells. Dose-dependent inhibition of cell growth was observed with an IC of approximately 150 μM BHA at 24 h. In addition, this agent-induced apoptosis, which was accompanied by the loss of mitochondrial membrane potential (ΔΨ) and caspase activation. Caspase-3 and -8 inhibitors markedly rescued HeLa cells from BHA-induced cell death. In addition, BHA decreased intracellular ROS levels in HeLa cells whereas it increased O levels among ROS. The number of glutathione (GSH)-depleted cells was increased in 150 μM BHA-treated cells, which was attenuated by caspase inhibitors. In conclusion, BHA inhibited the growth of HeLa cells via caspase-dependent apoptosis, which seemed to be related to increase in GSH depletion and O level. [ABSTRACT FROM AUTHOR]

Urotensin II (UII) is a vasoactive peptide with potent cardiovascular effects through a G protein-coupled receptor. Hypoxia stimulates the secretion of UII and atrial natriuretic peptide (ANP). However, the effect of UII on hypoxia-induced cardiac hypertrophy is still controversial. The present study was conducted to determine whether human UII (hUII)-mediated ANP secretion influences hypoxia-induced cardiac hypertrophy using in vitro and in vivo models. Hypoxia caused an increase in ANP secretion and a decrease in atrial contractility in isolated perfused beating rat atria. hUII (0.01 and 0.1 nM) attenuated hypoxia-induced ANP secretion without changing the atrial contractility, and the hUII effect was mediated by the UII receptor signaling involving phospholipase C, inositol 1,3,4 trisphosphate receptor, and protein kinase C. Rats treated with monocrotaline (MCT, 60 mg/kg) showed right ventricular hypertrophy with increases in pulmonary arterial pressure and its diameter and plasma levels of UII and ANP that were attenuated by the pretreatment with an UII receptor antagonist, urantide. An acute administration of hUII (5 μM injection plus 2.5 μM infusion for 15 min) decreased the plasma ANP level in MCT-treated rats but increased the plasma ANP level in MCT plus urantide-treated and sham-operated rats. These results suggest that hUII may deteriorate MCT-induced cardiac hypertrophy mainly through a vasoconstriction of the pulmonary artery and partly through the suppression of ANP secretion. [ABSTRACT FROM AUTHOR]

The proteasome inhibitor MG132 has been shown to induce apoptotic cell death through the formation of reactive oxygen species (ROS). Here, we investigated the molecular mechanisms of MG132 in As4.1 juxtaglomerular cell death in relation to apoptosis and levels of ROS and glutathione (GSH). MG132 inhibited the growth of As4.1 cells with an IC of approximately 0.3–0.4 μM at 48 h and induced cell death, accompanied by the loss of mitochondrial membrane potential (MMP; ∆Ψ), Bcl-2 decrease, activations of caspase-3 and caspase-8, and PARP cleavage. MG132 increased intracellular ROS levels and GSH-depleted cell numbers. However, caspase inhibitors, especially Z-VAD (pan-caspase inhibitor) intensified cell growth inhibition, cell death, MMP (∆Ψ) loss, and Bcl-2 decrease in MG132-treated As4.1 cells. Z-VAD also slightly intensified increases in ROS levels and GSH depletion in MG132-treated As4.1 cells. In conclusion, MG132 reduced the growth of As4.1 cells via caspase-independent apoptosis. The changes in ROS and GSH levels by MG132 and caspase inhibitors partially influenced the growth inhibition and death of As4.1 cells. [ABSTRACT FROM AUTHOR]

Pyrogallol (PG) induces apoptosis in several types of cells mediated by superoxide anion (O). Here, we investigated the effects of PG and/or MAPK (MEK, JNK, and p38) inhibitors on the changes in cell growth, cell death, reactive oxygen species (ROS), and GSH levels in As4.1 juxtaglomerular (JG) cells. PG inhibited the growth of As4.1 cells. It also induced apoptosis and the loss of mitochondrial membrane potential (MMP; ΔΨm) and increased the level of p53 protein. Intracellular O level was increased in PG-treated As4.1 cells. PG also increased the number of GSH deleted cells in As4.1 cells. All the MAPK inhibitors significantly attenuated the growth inhibition and death mediated by PG. They decreased the levels of p53 protein and MMP (ΔΨm) loss in PG-treated As4.1 cells. They also reduced O level and GSH-depleted cell number in these cells. In conclusion, MAPK inhibitors attenuated As4.1 cell growth inhibition and death mediated by PG treatment. The changes in O and GSH levels by PG and/or MAPK inhibitors appeared to affect the growth and death of As4.1 cells. [ABSTRACT FROM AUTHOR]

Carbobenzoxy-Leu-Leu-leucinal (MG132) as a proteasome inhibitor has been shown to induce apoptotic cell death through formation of reactive oxygen species (ROS). In the present study, we evaluated the effects of MG132 on the growth of A549 lung cancer cells in relation to cell growth, ROS and glutathione (GSH) levels. Treatment with MG132 inhibited the growth of A549 cells with an IC50 of approximately 20 μM at 24 hours. DNA flow cytometric analysis indicated that 0.5∼30 μM MG132 induced a G1 phase arrest of the cell cycle in A549 cells. Treatment with 10 or 30 μM MG132 also induced apoptosis, as evidenced by sub-G1 cells and annexin V staining cells. This was accompanied by the loss of mitochondrial membrane potential (MMP; ΔΨm). The intracellular ROS levels including O2∙- were strongly increased in 10 or 30 μM MG132-treated A549 cells but were down-regulated in 0.1, 0.5 or 1 mM MG132-treated cells. Furthermore, 10 or 30 μM MG132 increased mitochondrial O2∙- level but 0.1, 0.5 or 1 μM MG132 decreased that. In addition, 10 or 30 μM MG132 induced GSH depletion in A549 cells. In conclusion, MG132 inhibited the growth of human A549 cells via inducing the cell cycle arrest as well as triggering apoptosis, which was in part correlated with the changes of ROS and GSH levels. Our present data provide important information on the anti-growth mechanisms of MG132 in A549 lung cancer cells in relation to ROS and GSH. [ABSTRACT FROM AUTHOR]

Propyl gallate (PG) as a synthetic antioxidant is widely used in processed food, cosmetics and medicinal preparations. Despite the assumed low toxicity of PG, it exerts a variety of effects on tissue and cell functions. In the present study, we evaluated the anti-apoptotic effects of caspase inhibitors on PG-treated human cervix adenocarcinoma HeLa cells in relation to the changes of reactive oxygen species (ROS) and glutathione (GSH) levels. PG induced apoptosis in a dose-dependent manner, as evidenced by sub-G1 cells and annexin V staining cells. Treatment with pan-caspase inhibitor, caspase-3 inhibitor, caspase-8 inhibitor or caspase-9 inhibitor significantly prevented apoptosis in PG-treated HeLa cells at 24 h. The intracellular ROS levels including O were increased or decreased in PG-treated HeLa cells depending on the incubation times (1 or 24 h). PG depleted intracellular GSH content in HeLa cells at 24 h. Treatment with caspase inhibitor reduced ROS levels and significantly prevented GSH depletion in PG-treated HeLa cells at 24 h. In conclusion, PG induced apoptosis in HeLa cells. The anti-apoptotic effect of caspase inhibitor on PG-induced HeLa cell death was closely related to the reduction of ROS levels, especially mitochondrial O, as well as to the inhibition of GSH depletion. [ABSTRACT FROM AUTHOR]

2,4-Dinitrophenol (DNP) is an uncoupler of oxidative phosphorylation in mitochondria. Here, we investigated the in vitro effect of DNP on apoptosis and the involvement of reactive oxygen species (ROS) in As4.1 juxtaglomerular cell death. Dose- and time-dependent induction of apoptosis was evidenced by flow cytometric detection of sub-G1 DNA content and annexin V binding assay. The intracellular H2O2 and O2 ॱ- levels were markedly increased in DNP-treated cells. However, the reduction of intracellular H2O2 level by Tiron and catalase did not prevent apoptosis induced by DNP. Moreover, DNP rapidly reduced intracellular GSH content in As4.1 cells. Taken together, apoptosis in DNP-treated As4.1 cells is correlated with the rapid change of intracellular GSH levels rather than ROS levels. [Copyright &y& Elsevier]

Arsenic trixide (ATO) affects many biological processes sμch as cell proliferation, apoptosis, differentiation and an-giogenesis. L-bμthionine sμlfoximine (BSO) is an inhibitor of GSH synthesis. We tested whether ATO redμced the viability of lμng cancer A549 cells in vitro, and investigated the in vitro effect of the combination of ATO and BSO on cell viability in relation to apoptosis and the cell cycle. ATO caμsed a dose-dependant decrease of viability of A549 cells with an IC50 of more than 50 μM. Low doses of ATO or BSO (1-10 μM) alone did not indμce cell death. However, combined treatment depleted GSH content and indμced apoptosis, loss of mitochondrial transmembrane potential (ΔΨm) and cell cycle arrest in G2. Reactive oxygen species (ROS) increased or decreased depending on the concentration of ATO. In addition, BSO generally increased ROS in ATO-treated A549 cells. ROS levels were at least in part related to apoptosis in cells treated with ATO and/or BSO. In conclμsion, we have demonstrated that A549 lμng cells are very resistant to ATO, and that BSO synergizes with clinically achievable concentration of ATO. Oμr resμlts sμggest that combination treatment with ATO and BSO may be μsefμl for treating lμng cancer. [ABSTRACT FROM AUTHOR]

Arsenic trioxide (ATO) can affect many biological functions such as apoptosis and differentiation in various cells. We investigated the involvement of ROS and GSH in ATO-induced HeLa cell death using ROS scavengers, especially N-acetylcysteine (NAC). ATO increased intracellular O2•- levels and reduced intracellular GSH content. The ROS scavengers, Tempol, Tiron and Trimetazidine, did not significantly reduce levels of ROS or GSH depletion in ATO-treated HeLa cells. Nor did they reduce the apoptosis induced by ATO. In contrast, treatment with NAC reduced ROS levels and GSH depletion in the ATO-treated HeLa cells and prevented ATO-induced apoptosis. Treatment with exogenous SOD and catalase reduced the depletion of GSH content in ATO-treated cells. Catalase strongly protected the cells from ATO-induced apoptosis. In addition, treatment with SOD, catalase and NAC slightly inhibited the G1 phase accumulation induced by ATO. In conclusion, NAC protects HeLa cells from apoptosis induced by ATO by up-regulating intracellular GSH content and partially reducing the production of O2•-. [ABSTRACT FROM AUTHOR]

We investigated the in vitro effects of arsenic trioxide on cell growth, cell cycle regulation, and apoptosis in As4.1 juxtaglomerular cells. Arsenic trioxide inhibited the growth of As4.1 cells with an IC50 of ~5 µM. Arsenic trioxide induced S phase arrest of the cell cycle and very efficiently stimulated apoptosis in As4.1 cells, as evidenced by flow cytometric detection of sub-G1 DNA content, annexin V binding assay, and 4-6-diamidino-2-phenylindole staining. This apoptotic process was accompanied by the loss of mitochondrial transmembrane potential (ΔΨm), a decrease in Bcl-2, the activation of caspase-3, and cleavage of poly(ADP- ribose) polymerase. However, all of the caspase inhibitors tested in this experiment failed to rescue As4.1 cells from arsenic trioxide-induced cell death in view of sub-G, cells and annexin V positive- staining cells. However, a caspase-8 inhibitor (Z-IETD-FMK) noticeably decreased the loss of ΔΨm in arsenic trioxide-treated cells. When we examined the changes in reactive oxygen species (ROS), H2O2, or O2·- in arsenic trioxide-treated cells, H2O2 was significantly decreased and O2·- was increased. In addition, we detected a decreased OSH content in arsenic trioxide-treated cells. Taken together, we have demonstrated that arsenic trioxide as a ROS generator potently inhibited the growth of As4.1 JG cells through S phase arrest of the cell cycle and caspase-independent apoptosis. [ABSTRACT FROM AUTHOR]

Abstract. Acrylic quaternary copolymers (AQC) were synthesized from copolymerization reaction of 2-ethylhexyl acrylate (2-EHA), n-butyl acrylate (BA), ethyl acrylate (EA) and vinyl acetate (VAc). The blends of AQC with poly(vinyl chloride-co-vinyl acetate) (PVCVAc) and with poly(vinyl chloride-co-vinyl propionate) (PVCVP) were prepared by solution blending. Pressure sensitive adhesive (PSA) properties of AQC and their blends were investigated. Glass transition temperature Tg and holding power of AQC decreases with increasing contents of 2-EHA and BA. Tackiness, however, increases with increasing the contents of 2-EHA and BA. Peel strength shows maximum value for the sample with 15 wt% of those monomers. Tackiness of blend systems is similar, but holding power begins to decrease at 15 wt% or higher PVCVAc contents in AQC+PVCVAc blends. On the other hand, holding power of AQC+PVCVP blends increases as the contents of PVCVP increases. Failure modes of the blend are adhesive except for blends with 5 wt% of PVCVP. [ABSTRACT FROM AUTHOR]