Abstract Resveratrol is a naturally occurring phytoalexin with antioxidant and antiinflammatory properties. Recent studies suggest that resveratrol possesses anticancer effects, although its mechanism of action not well understood. We now show inhibits Src tyrosine kinase activity thereby blocks constitutive signal transducer activator transcription 3 (Stat3) protein activation in malignant cells. Analyses resveratrol-treated cells harboring constitutively-active Stat3 reveal irreversible...

IL-7 functions as a trophic factor during T lymphocyte development by mechanism that is partly based on the induction of Bcl-2, which protects cells from apoptosis. Here we report cytokine withdrawal activates prodeath protein Bax. On loss in dependent cell line, Bax translocated cytosol to mitochondria, where it integrated into mitochondrial membrane. This translocation was attributable conformational change itself. We show rise intracellular pH preceded and triggered conformation....

By utilizing RNA nanotechnology, we engineered both therapeutic siRNA and a receptor-binding aptamer into individual pRNAs of phi29's motor. The building block harboring or other molecules was fabricated subsequently trimer through the interaction right left interlocking loops. incubation protein-free nanoscale particles containing ligands resulted in binding co-entry trivalent cells, modulating apoptosis cancer cells leukemia model lymphocytes cell culture animal trials. use such...

Trophic factor withdrawal induces cell death by mechanisms that are incompletely understood.Previously we reported of interleukin-7 (IL-7) or IL-3 produced a rapid intracellular alkalinization, disrupting mitochondrial metabolism and activating the protein Bax.We now observe this novel alkalinization pathway is mediated pH regulator NHE1, as shown requirement for sodium, blocking pharmacological inhibitors use an NHE1-deficient line, altered phosphorylation NHE1.Alkalinization also required...

The antiapoptotic function of the interleukin-7 (IL-7) receptor is related to regulation three members Bcl2 family: synthesis Bcl2, phosphorylation Bad, and cytosolic retention Bax. Here we show that, in an IL-7-dependent murine T-cell line, different regions IL-7 initiate signal transduction pathways that regulate these proteins. Both Box1 Y449 are required Bax retention. This suggests a sequential model which Jak1, binds Box1, first activated then phosphorylates Y449, leading regulation,...

Herein, we report the use of a theranostic nanocarrier (Folate-HBPE(CT20p)) to deliver therapeutic peptide prostate cancer tumors that express PSMA (folate hydrolase 1). The (CT20p) targets and inhibits chaperonin-containing TCP-1 (CCT) protein-folding complex, is selectively cytotoxic cells, non-toxic normal tissue. With delivery CT20p cells via PSMA, dual level specificity achieved: (1) selective targeting PSMA-expressing tumors, (2) specific cytotoxicity with minimal toxicity cells....

Interleukin-7 (IL-7) is a cytokine that required for T cell development and survival. The anti-apoptotic function of IL-7 partly through induction Bcl-2 synthesis cytosolic retention Bax. Here we show the homology 3 domain-only protein, Bad, involved in death following withdrawal from D1 cells, an IL-7-dependent murine thymocyte line. stimulation resulted inactivation Bad by phosphorylation at Ser-112, -136, -155. phosphoinositide 3-kinase (PI3K)/Akt pathway has been implicated previously...

Interleukin (IL)-7 is required for survival and homeostatic proliferation of T lymphocytes. The effect IL-7 primarily through regulation Bcl-2 family members; however, the proliferative mechanism unclear. It has not been determined whether receptor actually delivers a signal or whether, by promoting survival, results from signals other than receptor. We show that in an IL-7–dependent cell line, cells protected apoptosis nevertheless underwent cycle arrest after withdrawal. This was...

// Ana C. Carr 1 , Amr S. Khaled 2 Rania Bassiouni Orielyz Flores Daniel Nierenberg Hammad Bhatti Priya Vishnubhotla J. Manuel Perez 3 Santimukul Santra 4 and Annette R. Burnett School of Biomedical Science, College Medicine, University Central Florida, Orlando, FL 32827, USA Department Pathology Laboratory Internal Orlando VA Medical Center, 32803, Imaging Research Institute, & Samuel Oschin Comprehensive Cancer Sciences Neurosurgery, Cedar Sinai Los Angeles, CA 90048, Chemistry,...

Metastatic disease is a leading cause of death for patients with breast cancer, driving the need new therapies. CT20p peptide previously discovered by our group that displays cancer-specific cytotoxicity. To design optimal therapeutic use peptide, we identified intracellular target in cancer cells, correlating expression patterns susceptibility to CT20p.Using polymeric nanoparticles deliver CT20p, assessed cytoskeletal changes, cell migration, adhesion, and viability cells treated peptide....

Chaperonin-containing TCP-1 (CCT or TRiC) is a multi-subunit complex that folds many of the proteins essential for cancer development. CCT expressed in diverse cancers and could be an ideal therapeutic target if not fact encoded by eight distinct genes, complicating development inhibitors. Few definitive studies addressed role specific subunits promoting chaperonin's function cancer. To this end, we investigated activity CCT2 (CCTβ) overexpressing depleting subunit breast epithelial cells....

The cytokine interleukin-7 (IL-7) has essential growth activities that maintain the homeostatic balance of immune system. Little is known mechanism by which IL-7 signaling regulates metabolic activity in support its vital function lymphocytes. We observed deprivation caused a rapid decline metabolism glucose was attributable to loss intracellular retention. To identify transducer signal, we examined expression three important regulators metabolism, transporter GLUT-1 and two glycolytic...

Abstract Breast cancer (BC) recurrence and metastasis are significant causes of death, mainly due to the emergence therapy-resistant cells. Secreted factors known as extracellular vesicles (EVs), especially small EVs (SEVs) or exosomes less than 100 nanometers in size, have been implicated plasticity associated with drug resistance, BC recurrence, metastasis. derived from cells can transform local distal non-tumor cells, induce epithelial-to-mesenchymal transition, trigger uncontrolled...

Lymphocytes are the central mediators of immune response, requiring cytokines for survival and proliferation. Survival signaling targets Bcl-2 family apoptotic mediators, however, pathway cytokine-driven proliferation lymphocytes is poorly understood. Here we show that cytokine-induced cell cycle progression not solely dependent on synthesis cyclin-dependent kinases (Cdks) or cyclins. Rather, observe in lymphocyte lines interleukin-3 interleukin-7, primary interleukin 7, phosphatase Cdc25A...