Abstract The tumor suppressor p53 binds prosurvival Bcl-2 family proteins such as Bcl-w and Bcl-XL to liberate Bax, which in turn exerts proapoptotic or anti-invasive functions depending on stress context. On the basis of our previous finding that interacts with p21, we investigated possible involvement p21 these functions. Here, report although can bind alone, it requires Bax suppress cell invasion promote death. bound Bcl-w, forming a p53/p21/Bcl-w complex manner maintained all pairwise...

Monocyte apoptosis has emerged as a central regulatory event in hemopoiesis and inflammation. Inflammatory cytokines can either promote or prevent monocyte apoptosis. To study the possible role of Fas Ag, member TNF/nerve growth factor receptor family, apoptosis, human peripheral blood monocytes activated by IL-1 beta TNF-alpha were exposed to anti-Fas mAb. Engagement Ag resulted monocytes, monitored propidium iodide uptake, decrease cell size, DNA fragmentation, characteristic...

Although mitochondria and the Nox family of NADPH oxidase are major sources reactive oxygen species (ROS) induced by external stimuli, there is limited information on their functional relationship. This study has shown that serum withdrawal promotes production ROS in human 293T cells stimulating both Nox1. An analysis relationship revealed respond to within a few minutes, produced trigger Nox1 action phosphoinositide 3-kinase (PI3K) Rac1. Activation PI3K/Rac1/Nox1 pathway was evident 4-8 h...

Abstract Given a previous report that Bcl-w is expressed in gastric cancer cells, particularly those of an infiltrative morphology, we investigated whether expression influences the invasiveness cells. To accomplish this, was overexpressed adherent types adenocarcinoma cell lines, and this found to result increase their migratory invasive potentials. These effects were not induced when Bcl-2 same types. Consistently, Bcl-w, but Bcl-2, overexpression increased matrix metalloproteinase-2...

Bmal1 is a core factor in the regulation of circadian rhythms. Previous studies have shown that suppresses tumor growth cell culture and animal models downregulated certain types cancer. The aim present study was to investigated whether influences invasiveness cancer cells. We demonstrated knockdown by RNA interference promoted invasion, whereas its overexpression reduced cellular invasiveness. These effects were observed lung glioma cells, occurred regardless p53 status. Therefore, it...

We previously reported that podophyllotoxin acetate (PA) radiosensitizes NCI-H460 cells. Here, we confirmed PA treatment also induces cell death among two other non-small lung cancer (NSCLC) lines: NCI-H1299 and A549 cells (IC50 values = 7.6 16.1 nM, respectively). Our experiments further showed was able to induce via various mechanisms. First, dose-dependently induced cycle arrest at G2/M phase, as shown by accumulation of the mitosis-related proteins, p21, survivin Aurora B. This phase due...

Abstract Peroxiredoxins (PRDX) are a family of thiol-dependent peroxidases. Among the six mammalian members this family, PRDX6 is only protein that additionally exhibits phospholipase A2 (PLA2) activity. The physiologic role interesting feature largely unknown at present. In study, we show increases metastatic potential lung cancer cells. Functional analyses enzymatic activities PRDX6, using specific pharmacologic inhibitors and mutagenesis studies, reveal both peroxidase PLA2 required for...

Previous reports suggest that, in addition to its therapeutic effects, ionizing radiation (IR) increases the invasiveness of surviving cancer cells. Here, we demonstrate that this activity IR lung cells is mediated by a signaling pathway involving p38 kinase, phosphoinositide 3-kinase, Akt, and matrix metalloproteinase (MMP-2). The invasion-promoting doses also increased reduced levels vimentin E-cadherin, respectively, both which are markers for epithelial-mesenchymal transition (EMT)....

Although much is known about interleukin (IL)-1β and its role as a key mediator of cartilage destruction in osteoarthritis, only limited information available on IL-1β signaling chondrocyte dedifferentiation. Here, we have characterized the molecular mechanisms leading to dedifferentiation primary cultured articular chondrocytes by treatment. or lipopolysaccharide, but not phorbol 12-myristate 13-acetate, retinoic acid, epidermal growth factor, induced nicotinamide phosphoribosyltransferase...

Abstract Background Γ-Ionizing radiation (IR) therapy is one of major therapeutic tools in cancer treatment. Nevertheless, γ-IR failed due to occurrence metastasis, which constitutes a significant obstacle The main aim this investigation was construct animal model present metastasis during radiotherapy mouse system vivo and establishes the molecular mechanisms involved. Materials methods C6L transfectant cell line expressing firefly luciferase (fLuc) treated with γ-IR, followed by...

Abstract Procollagen-lysine, 2-oxoglutarate 5-dioxygenase (PLOD3), a membrane-bound homodimeric enzyme, hydroxylates lysyl residues in collagen-like peptides; however, its role lung cancer is unknown. This study aimed to investigate the of PLOD3 as pro-metastatic factor and elucidate underlying mechanism. First, we experimentally confirmed release circulation animal models, rendering it potential serum biomarker for humans. Thereafter, investigated effects overexpression downregulation on...

To improve radiation therapy, the development of effective radiosensitizer is required. Fifty percent inhibitory concentration (IC50) values 3',4',5',7'‑tetrahydroxyflavone (luteolin) against NCI‑H460 and ‑H1299 non‑small cell lung cancer (NSCLC) cells were determined using 3‑(4,5‑dimethylthiazol‑2‑yl)‑2,5‑diphenyltetrazolium bromide (MTT) assays. Radiosensitizing activity was assessed in vitro by treating with luteolin prior to irradiation γ‑ionizing (IR), performing count clonogenic Cell...

The nature of the molecules underlying radioresistance phenotype laryngeal cancer cells remains to be established. We initially generated radioresistant cell lines from human HEp-2 with fractionated radiation. These RR-HEp-2 and isolated clones displayed more anti-apoptotic phenotypes than parental after Characteristics RR-Hep-2 were confirmed by upregulation radioresistance-related genes, such as epidermal growth factor receptor, Hsp90, Bcl-xl. Subsequently, we examined proteome changes...

Here, we report a new intracellular signaling pathway involved in γ-ionizing radiation (IR)-induced migration/invasion and show that podophyllotoxin acetate (PA) inhibits the IR-induced invasion migration of A549 cells (a non-small cell lung cancer (NSCLC) line). Our results revealed IR increased invasion/migration cells, this effect was decreased by 10 nM PA treatment. also inhibited expressions/activities matrix metalloprotase (MMP) -2, MMP-9, vimentin, suggesting could block...

Although end-binding protein 1 (EB1) is well known to regulate microtubule dynamics, the role of EB1 in apoptosis non-small cell lung cancer (NSCLC) poorly understood. Here, we investigated molecular mechanism by which regulates H460, A549, and H1299 cells. Depletion A549 cells, express high levels EB1, induced death a p53-independent manner through over-production reactive oxygen species (ROS) Bax induction. This phenomenon was potentiated radiation-treated EB1-knockdown cells largely...

Low levels of H2O2 can induce cellular resistance to subsequent higher H2O2. By using human U937 leukemia cells, it was previously shown that such an adaptive response be induced without increasing the capacity degrade H2O2, thus conferring on cells a cross-resistance other stimuli as serum withdrawal and C2-ceramide. In this study, found stress-activated protein kinase/c-Jun N-terminal kinase (SAPK/JNK) acts common mediator cell death by high concentrations, Although SAPK/JNK activation...

The peroxiredoxin family of peroxidase has six mammalian members (Prx 1–6). Considering their frequent up-regulation in cancer cells, Prxs may contribute to cells' survival face oxidative stress. Here, we show that Prx 6 promotes the invasiveness lung accompanied by an increase activity phosphoinositide 3-kinase (PI3K), phosphorylation p38 kinase and Akt, protein levels uPA. Functional studies reveal these components support 6-induced invasion sequence kinase/PI3K, findings provide a new...