Agonist-induced 4-1BB activation prevents the development of Sjӧgren's syndrome-like sialadenitis in non-obese diabetic mice.

Activation of costimulatory receptor 4-1BB enhances T helper 1 (Th1) and CD8 T cell responses in protective immunity, and prevents or attenuates several autoimmune diseases by increasing Treg numbers and suppressing Th17 or Th2 effector response. We undertook this study to elucidate the impact of enforced 4-1BB activation on the development of Sjögren's syndrome (SS)-like sialadenitis in non-obese diabetic (NOD) model of this disease. An anti-4-1BB agnostic antibody was intraperitoneally injected to female NOD mice aged 7 weeks, prior to the disease onset that occurs around 10-11 weeks of age, 3 times weekly for 2 weeks, and the mice were analyzed for SS pathologies at age 11 weeks.

Suberoylanilide hydroxamic acid induces thioredoxin1-mediated apoptosis in lung cancer cells via up-regulation of miR-129-5p.

Histone deacetylase (HDAC) inhibitors, especially suberoylanilide hydroxamic acid (SAHA) induce apoptosis in various cancer cells. Here, we investigated the effect of SAHA on apoptosis in lung cancer cells and addressed the role of reactive oxygen species (ROS), glutathione (GSH), and thioredoxin1 (Trx1) levels in this process. We also identified the miRNAs that down-regulate Trx1 expression at RNA level and thereby influence apoptotic cell death of SAHA increased intracellular ROS levels and promoted apoptotic cell death in cancerous cells but not in non-cancerous normal lung cells.

Suberoylanilide hydroxamic acid increases anti-cancer effect of tumor necrosis factor-α through up-regulation of TNF receptor 1 in lung cancer cells.

Suberoylanilide hydroxamic acid (SAHA) as a histone deacetylase (HDAC) inhibitor has anti-cancer effect. Here, we evaluated the effect of SAHA on HDAC activity and cell growth in many normal lung and cancer cells. We observed that the HDAC activities of lung cancer cells were higher than that of normal lung cells.

The levels of HDAC1 and thioredoxin1 are related to the death of mesothelioma cells by suberoylanilide hydroxamic acid.

Mesothelioma is an aggressive tumor which is mainly derived from the pleura of lung. In the present study, we evaluated the anticancer effect of suberoylanilide hydroxamic acid (SAHA), a histone deacetylase (HDAC) inhibitor on human mesothelioma cells in relation to the levels of HDAC1, reactive oxygen species (ROS) and thioredoxin (Trx). While 1 µM SAHA inhibited cell growth in Phi and ROB cells at 24 h, it did not affect the growth in ADA and Mill cells.

Antimycin A induces death of the human pulmonary fibroblast cells via ROS increase and GSH depletion.

Antimycin A (AMA) inhibits the growth of various cells via stimulating oxidative stress-mediated death. However, little is known about the anti-growth effect of AMA on normal primary lung cells. Here, we investigated the effects of AMA on cell growth inhibition and death in human pulmonary fibroblast (HPF) cells in relation to reactive oxygen species (ROS) and glutathione (GSH) levels.

Auranofin induces mesothelioma cell death through oxidative stress and GSH depletion.

Mesothelioma is an aggressive tumor associated with asbestos exposure. Auranofin as an inhibitor of thioredoxin reductase (TrxR) affects many biological processes such as inflammation and proliferation. In the present study, we investigated the cellular effects of auranofin on patient-derived mesothelioma cells in relation to reactive oxygen species (ROS) and glutathione (GSH) levels.

Down-Regulation of Thioredoxin1 Is Involved in Death of Calu-6 Lung Cancer Cells Treated With Suberoyl Bishydroxamic Acid.

Suberoyl bishydroxamic acid (SBHA), a histone deacetylase (HDAC) inhibitor, can show an anticancer effect. In this study, we investigated the effects of SBHA on the growth inhibition and death of Calu-6 and NCI-H1299 cells in relation to reactive oxygen species (ROS) and antioxidant levels. SBHA inhibited the growth of Calu-6 and NCI-H1299 lung cancer cells with an IC50 of 50 µM at 72 h.

Reactive oxygen species, glutathione, and thioredoxin influence suberoyl bishydroxamic acid-induced apoptosis in A549 lung cancer cells.

Suberoyl bishydroxamic acid (SBHA) as a histone deacetylase (HDAC) inhibitor can induce apoptosis through the formation of reactive oxygen species (ROS). However, there is no report about the regulation of ROS and antioxidant enzymes in SBHA-treated lung cancer cells. Here, we investigated the toxicological effects of SBHA on the regulations of ROS, glutathione (GSH), and antioxidant enzymes, especially thioredoxin (Trx) in A549 lung cancer cells.

PX-12 induces apoptosis in Calu-6 cells in an oxidative stress-dependent manner.

PX-12 (1-methylpropyl 2-imidazolyl disulfide) as a thioredoxin (Trx) inhibitor has an anti-tumor effect. However, there is no report about the toxicological effect of PX-12 on lung cancer cells. Here, we investigated the anti-growth effects of PX-12 on Calu-6 lung cancer cells in relation to reactive oxygen species (ROS) and glutathione (GSH) levels.

Auranofin induces apoptosis and necrosis in HeLa cells via oxidative stress and glutathione depletion.

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.

Suberoylanilide hydroxamic acid-induced HeLa cell death is closely correlated with oxidative stress and thioredoxin 1 levels.

Suberoylanilide hydroxamic acid (SAHA) is a histone deacetylase (HDAC) inhibitor which has anticancer effects. We evaluated the growth inhibitory effects of SAHA on HeLa cervical cancer cells in relation to reactive oxygen species (ROS) levels. SAHA inhibited the growth of HeLa cells with an IC(50) of approximately 10 µM at 24 h, and induced apoptosis which was accompanied by the cleavage of PARP, caspase-3 activation and loss of mitochondrial membrane potential (MMP; ∆ψ(m)).

Vaccination with a piggyBac plasmid with transgene integration potential leads to sustained antigen expression and CD8(+) T cell responses.

DNA vaccination with plasmid has conventionally involved vectors designed for transient expression of antigens in injected tissues. Next generation plasmids are being developed for site-directed integration of transgenes into safe sites in host genomes and may provide an innovative approach for stable and sustained expression of antigens for vaccination. The goal of this study was to evaluate in vivo antigen expression and the generation of cell mediated immunity in mice injected with a non-integrating plasmid compared to a plasmid with integrating potential.

PX-12-induced HeLa cell death is associated with oxidative stress and GSH depletion.

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.

PX-12 inhibits the growth of A549 lung cancer cells via G2/M phase arrest and ROS-dependent apoptosis.

PX-12 (1-methylpropyl 2-imidazolyl disulfide) is an inhibitor of thioredoxin (Trx-1), which has antitumor effects. However, little is known about the toxicological effect of PX-12 on cancer cells. We investigated the anti-growth effects of PX-12 on A549 lung cancer cells in relation to reactive oxygen species (ROS) and glutathione (GSH) levels.

Valproic acid inhibits the growth of HeLa cervical cancer cells via caspase-dependent apoptosis.

Valproic acid (VPA) as a histone deacetylase (HDAC) inhibitor has an anticancer effect. In the present study, we evaluated the effects of VPA on the growth and death of HeLa cervical cancer cells in relation to reactive oxygen species (ROS) and glutathione (GSH). Dose- and time-dependent growth inhibition was observed in HeLa cells with an IC50 of approximately 10 mM at 24 h.

Zebularine inhibits the growth of A549 lung cancer cells via cell cycle arrest and apoptosis.

Zebularine (Zeb) is a DNA methyltransferase (DNMT) inhibitor to that has an anti-tumor effect. Here, we evaluated the anti-growth effect of Zeb on A549 lung cancer cells in relation to reactive oxygen species (ROS) levels. Zeb inhibited the growth of A549 cells with an IC50 of approximately 70 µM at 72 h.

Zebularine-induced apoptosis in Calu-6 lung cancer cells is influenced by ROS and GSH level changes.

Zebularine (Zeb) is a DNA methyltransferase (DNMT) inhibitor that has various biological properties including anti-cancer effect. In the present study, we evaluated the effects of Zeb on the growth and death of Calu-6 lung cancer cells in relation to reactive oxygen species (ROS) and glutathione (GSH) levels. Zeb inhibited the growth of Calu-6 cells with an IC50 of approximately 150 μM at 72 h in a dose-dependent manner.

Suberoyl bishydroxamic acid-induced apoptosis in HeLa cells via ROS-independent, GSH-dependent manner.

Suberoyl bishydroxamic acid (SBHA) is a HDAC inhibitor that can regulate many biological functions including apoptosis and proliferation in various cancer cells. Here, we evaluated the effect of SBHA on the growth of HeLa cervical cancer cells in relation to apoptosis, reactive oxygen species (ROS) and glutathione (GSH) levels. Dose-dependent inhibition of cell growth was observed in HeLa cells with an IC50 of approximately 15 μM at 72 h.

Trichostatin A induces apoptotic cell death of HeLa cells in a Bcl-2 and oxidative stress-dependent manner.

Trichostatin A (TSA) as a HDAC inhibitor can regulate many biological properties including apoptosis and cell proliferation in various cancer cells. Here, we evaluated the effect of TSA on the growth and death of HeLa cervical cancer cells in relation to reactive oxygen species (ROS) and glutathione (GSH) levels. Dose- and time-dependent growth inhibition was observed in HeLa cells with an IC50 of approximately 20 nM at 72 h.

Zebularine inhibits the growth of HeLa cervical cancer cells via cell cycle arrest and caspase-dependent apoptosis.

Zebularine (Zeb) as a DNA methyltrasferase (DNMT) inhibitor has various cellular effects such as cell growth inhibition and apoptosis. In the present study, we evaluated the effects of Zeb on the growth and death of HeLa cervical cancer cells. Zeb inhibited the growth of HeLa cells with an IC(50) of approximately 130 μM at 72 h in a dose-dependent manner.

Arsenic trioxide induces human pulmonary fibroblast cell death via increasing ROS levels and GSH depletion.

Arsenic trioxide (ATO; As2O3) induces apoptotic cell death in various cancer cells including lung cancer via the induction of reactive oxygen species (ROS). However, little is known about the toxicological effects of ATO on normal primary lung cells. Here, we investigated the effects of N-acetyl cysteine (NAC) and vitamin C (well-known antioxidants) or L-buthionine sulfoximine (BSO; an inhibitor of GSH synthesis) on ATO-treated human pulmonary fibroblast (HPF) cells in relation to cell death, ROS and glutathione (GSH).

Gallic acid-induced lung cancer cell death is accompanied by ROS increase and glutathione depletion.

Gallic acid (GA) is generally distributed in a variety of plants and foods, and its various biological effects have been reported. Here, we investigated the effects of GA and/or caspase inhibitors on Calu-6 and A549 lung cancer cells in relation to cell death and reactive oxygen species (ROS). The growths of Calu-6 and A549 cells were diminished with an IC(50) of approximately 30 and 150 μM GA at 24 h, respectively.

The MEK inhibitor PD98059 attenuates growth inhibition and death in gallic acid-treated Calu-6 lung cancer cells by preventing glutathione depletion.

Gallic acid (GA) is widely distributed in various plants and foods and has various biological effects. In this study, we investigated the effects of mitogen-activated protein kinase (MEK, JNK or p38) inhibitors on GA-induced Calu-6 lung cancer cell death in relation to reactive oxygen species (ROS) and glutathione (GSH) levels. GA inhibited the growth of Calu-6 cells and induced apoptosis and/or necrosis accompanied by the loss of mitochondrial membrane potential (MMP; Δψm).

Proteasome inhibition by MG132 induces growth inhibition and death of human pulmonary fibroblast cells in a caspase-independent manner.

MG132 as a proteasome inhibitor that can induce apoptotic cell death in various cell types including lung cancer cells. We investigated the cellular effects of MG132 on human pulmonary fibroblast (HPF) cells in relation to cell growth inhibition and death, and described the molecular mechanisms of MG132 in HPF cell death. This agent dose-dependently inhibited the growth of HPF cells with an IC50 of approximately 20 µM at 24 h and induced cell death accompanied by the loss of mitochondrial membrane potential (MMP; ∆Ψm) and an increase in caspase-3 and -8 activities.

The enhancement of propyl gallate-induced apoptosis in HeLa cells by a proteasome inhibitor MG132.

Propyl gallate (PG) used in processed food and medicinal preparations has been shown to induce cell death in normal and cancer cells. The inhibition of proteasome function has emerged as a useful strategy to maneuver apoptosis. Here, we investigated the combined effects of PG and MG132 (a proteasome inhibitor) on HeLa cells in relation to cell growth, cell death, reactive oxygen species (ROS) and glutathione (GSH).