PURPOSE Prosurvival Bcl-2 proteins inhibit the mitochondrial and death receptor-mediated apoptotic pathways. Obatoclax is a small-molecule antagonist of the BH3-binding groove of Bcl-2 proteins that may enhance tumor necrosis factor-related apoptosis-inducing ligand (TRAIL) sensitivity and efficacy. EXPERIMENTAL DESIGN Human pancreatic cancer cell lines were incubated with obatoclax and/or TR...

Programmed necrosis induced by DNA alkylating agents, such as MNNG, is a caspase-independent mode of cell death mediated by apoptosis-inducing factor (AIF). After poly(ADP-ribose) polymerase 1, calpain, and Bax activation, AIF moves from the mitochondria to the nucleus where it induces chromatinolysis and cell death. The mechanisms underlying the nuclear action of AIF are, however, largely unkn...

Our previous study demonstrated that CopA3, a disulfide dimer of the coprisin peptide analogue (LLCIALRKK), has antibacterial activity. In this study, we assessed whether CopA3 caused cellular toxicity in various mammalian cell lines. CopA3 selectively caused a marked decrease in cell viability in Jurkat T, U937, and AML-2 cells (human leukemia cells), but was not cytotoxic to Caki or Hela cell...

This study is the first to investigate the anticancer effect of dehydrocostuslactone [DHE (3aS,6aR,9aR,9bS)-decahydro-3,6,9-tris(methylene) azuleno[4,5-b]furan-2(3H)-one)], a medicinal plant-derived sesquiterpene lactone, on hepatocellular carcinoma. Our results showed that DHE inhibits the proliferation of HepG2 and PLC/PRF/5 cells by inducing apoptosis. DHE induces up-regulation of Bax and Ba...

Apoptosis Inducing Factor (AIF) is a highly conserved, ubiquitous flavoprotein localized in the mitochondrial intermembrane space. In vivo, AIF provides protection against neuronal and cardiomyocyte apoptosis induced by oxidative stress. Conversely in vitro, AIF has been demonstrated to have a pro-apoptotic role upon induction of the mitochondrial death pathway, once AIF translocates to the nuc...

Heat shock protein 70 (HSP70) inhibits apoptosis and thereby increases the survival of cells exposed to a wide range of lethal stimuli. HSP70 has also been shown to increase the tumorigenicity of cancer cells in rodent models. The protective function of this chaperone involves interaction and neutralization of the caspase activator apoptotic protease activation factor-1 and the mitochondrial fl...

Intestinal ischemia after trauma-hemorrhagic shock (T/HS) results in gut barrier dysfunction and the production/release of biologically active and tissue injurious factors in the mesenteric lymph, which, in turn, causes acute lung injury and a systemic inflammatory state. Since T/HS-induced lung injury is associated with pulmonary endothelial and epithelial cell programmed cell death (PCD) and ...

When overexpressed, the stress protein heat shock protein 70 (HSP70) increases the oncogenic potential of cancer cells in rodent models. HSP70 also prevents apoptosis, thereby increasing the survival of cells exposed to a wide range of otherwise lethal stimuli. These protective functions of HSP70 involve its interaction with and neutralization of the adaptor molecule apoptotic protease activati...

Loss of mitochondrial membrane integrity and release of apoptogenic factors are a key step in the signaling cascade leading to neuronal cell death in various neurological disorders, including ischemic injury. Emerging evidence has suggested that the intramitochondrial protein apoptosis-inducing factor (AIF) translocates to the nucleus and promotes caspase-independent cell death induced by gluta...

Poly (ADP-ribose) polymerase (PARP) has been proposed to play an important role in the pathogenesis of heart ischaemia/reperfusion (I/R) injury. However, the mechanisms of PARP-mediated heart I/R injury in vivo are still not thoroughly understood. Therefore, in this study, we investigate the effect of PARP inhibition on heart I/R injury and try to elucidate the underlying mechanisms. Studies we...