As a pro-apoptotic factor, prostate apoptosis response protein 4 (par-4) was first found in the male hormone-dependent prostate cells (AT-3). Endogenous Par-4 sensitizes cancer cells to apoptotic stimuli, but exogenous Par-4 selectively induces apoptosis in cancer cells, and these activities depends on the structure of its core domain SAC. Par-4 and SAC can specifically induce apoptosis of cancer cells but not of normal cells, and are therefore potential anti-cancer drugs. In this review we summarize the discovery, structure, and function of par-4, and its intracellular signaling pathways, then discuss the application prospects of Par-4 and SAC in the clinical treatment of cancer and the problems in its research and clinical applications.
Apoptosis ; Apoptosis Regulatory Proteins ; metabolism ; Humans ; Tumor Suppressor Proteins

Apoptosis and autophagy are important molecular processes that maintain organismal and cellular homeostasis, respectively. While apoptosis fulfills its role through dismantling damaged or unwanted cells, autophagy maintains cellular homeostasis through recycling selective intracellular organelles and molecules. Yet in some conditions, autophagy can lead to cell death. Apoptosis and autophagy can be stimulated by the same stresses. Emerging evidence indicates an interplay between the core proteins in both pathways, which underlies the molecular mechanism of the crosstalk between apoptosis and autophagy. This review summarizes recent literature on molecules that regulate both the apoptotic and autophagic processes.
Animals ; Apoptosis ; Apoptosis Regulatory Proteins ; metabolism ; Autophagy ; Homeostasis ; Humans ; Neoplasms ; metabolism ; pathology ; Signal Transduction

The objective of this study was to estimate a novel apoptosis-promoting molecule PDCD5 expression in the bone marrow cells from adult acute myeloid leukemia (AML) for investigation of its significance in the pathogenesis of AML. Flow cytometry assay was used for detection of PDCD5 expression in the different groups of cells from bone marrow of AML patients and normal controls by using 21 monoclonal antibodies with different fluorescent markers. The PDCD5 expressions in bone marrow cells from some AML patients and normal controls were also detected by Western blot. The results showed that the mean PDCD5 fluorescence intensity in bone marrow nucleated cells (MNC) from the bone marrow of 36 untreated AML patients was significantly lower than that from the bone marrow of 30 normal controls (3059 +/- 1392) vs (7432 +/- 1261) (P < 0.01). The mean PDCD5 fluorescence intensity was lower in the marrow granulocytes, monocytes, blast cells, and lymphocytes from untreated AML patients than that from normal (3939 +/- 2121) vs (8367 +/- 1045); (3156 +/- 1635) vs (5917 +/- 2329); (2824 +/- 1592) vs (3998 +/- 2106); (1474 +/- 816) vs (3355 +/- 2042) respectively, (all P < 0.01). Western blot analysis demonstrated that PDCD5 expression was significantly decreased in the AML cells, as compared with normal cells. It is concluded that PDCD5 expression in MNC in untreated AML patients is lower than that in the normal. PDCD5 expression in the marrow granulocytes, monocytes, blast cells, and lymphocytes of untreated AML patients is significantly lower than that in the normal. It suggests that the abnormally low expression of PDCD5 may be involved in the pathogenesis of AML.
Apoptosis ; physiology ; Apoptosis Regulatory Proteins ; metabolism ; Bone Marrow Cells ; metabolism ; Humans ; Leukemia, Myeloid, Acute ; metabolism ; pathology ; Neoplasm Proteins ; metabolism

The inflammasome is a group of multiprotein complexes in the cytoplasm, which can activate caspase-1 that mediates the maturation and release of IL-1β, IL-18, IL-33 and other pro-inflammatory cytokines.NALP1 (NACHT leucine-rich-repeat protein 1), also known as NLRP1, is the first one of the identified complex inflammasomes with definite ligands mainly involved in the activation of inflammasome assembly and the formation of apoptotic bodies. Moreover, it was also found that NLRP1 plays an important biological role in the development of acute leukemia, the bone marrow hematopoietic stem cell apoptosis and other blood diseases. This review briefly summarizes the structure, activation mechanism, regulation and the role of NLRP1 in the hematopoietic system.
Adaptor Proteins, Signal Transducing ; metabolism ; Apoptosis ; Apoptosis Regulatory Proteins ; metabolism ; Cytokines ; Hematologic Diseases ; metabolism ; pathology ; Humans ; Inflammasomes ; Multiprotein Complexes

OBJECTIVETo study the regulation of luteolin on spleen cells and sarcoma S180 cells in normal ICR mice.

METHODSSpleen cells and S180 cells were incubated with different concentrations of luteolin (50, 100, 200, and 400 μmol/L). The effect of luteolin on spleen cells and sarcoma S180 cells was determined by MTT assay. The apoptosis was detected using propidium iodide staining flow cytometry. Intracellular reactive oxygen species (ROS) was determined by flow cytometric analysis. Activities of free radicals scavenging were determined by hydroxyl radical and DPPH tests.

RESULTSCompared with the solvent control group, 200 and 400 μmol/L luteolin increased the spleen cells viability (P < 0.05). Luteolin at 100, 200, and 400 μmol/L decreased activities of S180 cells (P < 0.01). The proportion of sub-G1 phase spleen cells was reduced after treated with 200 and 400 μmol/L luteolin (P < 0.05). The proportion of sub-G1 phase S180 cells was elevated after treated with 200 and 400 μmol/L luteolin (P < 0.05). Compared with the solvent control group, levels of intracellular ROS in spleen cells of ICR mice all increased; levels of intracellular ROS in S180 cells all decreased after treated with 50, 100, 200, and 400 μmol/L luteolin (P < 0.05). Luteolin scavenged hydroxyl radical and DPPH in a dose dependent manner.

CONCLUSIONLuteolin had bilateral regulation on viability and apoptosis of spleen cells and S180 cells (promoting the viability of spleen cells, inhibiting apoptosis of spleen cells, inhibiting the viability of S180 cells, and promoting apoptosis of S180 cells), which was worth further study and exploration.

Animals ; Apoptosis ; Apoptosis Regulatory Proteins ; metabolism ; Cell Survival ; Luteolin ; metabolism ; Mice ; Mice, Inbred ICR ; Reactive Oxygen Species ; Sarcoma ; Spleen ; metabolism

OBJECTIVETo investigate the role of apoptosis stimulating protein 2 of p53 (ASPP2) phosphorylation status in the regulation of ASPP2-p53 apoptotic pathway activity.

METHODSCells were individually transfected with green fluorescent protein (GFP)-encoding vector, constitutively non-phosphorylatable ASPP2 mutant-ASPP2 (Am)-encoding vector, and wild type ASPP2 (Aw)-encoding vector) plasmids, respectively, to make them overexpressing phosphorylated and non-phosphorylated ASPP2 proteins, respectively. Cell apoptosis was induced by oxaliplatin. The apoptosis rate of cells was determined by flow cytometry after staining with FITC-conjugated annexin V and PI. ASPP2 protein level and its phosphorylation status were observed by Western blot. The interaction between ASPP2 and p53 was observed by immunoprecipitation assay.

RESULTSOxaliplatin induced cell apoptosis and caused phosphorylation of ASPP2 at ser92/ser361 in the HCT116 cells. The apoptosis rate of Aw and Am plasmids-transfected cells were (3.8 ± 1.0)% and (3.9 ± 1.2)% respectively, statistically with a non-significant difference (P > 0.05) in comparison with that of the GFP plasmid-transfected cells [(4.0 ± 0.8)%]. After oxaliplatin treatment, the apoptosis rate of Aw plasmid-transfected cells was (46.7 ± 3.9)%, significantly higher than that of the Am and GFP plasmid-transfected cells [(40.1 ± 10.2)% and (37.1 ± 6.9)%, respectively, P < 0.05], however, there was no statistically significant difference (P > 0.05) between Am and GFP plasmid-transfected cells. These results indicate that phosphorylated ASPP2 promoted the oxaliplatin-induced apoptosis of HCT116 cells through a p53-dependent pathway. Phosphorylation status of ASPP2 influenced its binding activity to p53.

CONCLUSIONPhosphorylation status of ASPP2 modulates p53 apoptotic function in oxaliplatin-induced apoptosis of colorectal cancer HCT116 cells.

Apoptosis ; Apoptosis Regulatory Proteins ; metabolism ; Colorectal Neoplasms ; metabolism ; HCT116 Cells ; Humans ; Organoplatinum Compounds ; Phosphorylation ; Tumor Suppressor Protein p53 ; genetics ; metabolism

Recent advances in the understanding of the molecular processes contributing to autophagy have provided insight into the relationship between autophagy and apoptosis. In contrast to the concept of "autophagic cell death," accumulating evidence suggests that autophagy serves a largely cytoprotective role in physiologically relevant conditions. The cytoprotective function of autophagy is mediated in many circumstances by negative modulation of apoptosis. Apoptotic signaling, in turn, serves to inhibit autophagy. While the mechanisms mediating the complex counter-regulation of apoptosis and autophagy are not yet fully understood, important points of crosstalk include the interactions between Beclin-1 and Bcl-2/Bcl-xL and between FADD and Atg5, caspase- and calpain-mediated cleavage of autophagy-related proteins, and autophagic degradation of caspases. Continued investigation of these and other means of crosstalk between apoptosis and autophagy is necessary to elucidate the mechanisms controlling the balance between survival and death both under normal conditions and in diseases including cancer.
Animals ; Apoptosis ; physiology ; Apoptosis Regulatory Proteins ; metabolism ; Autophagy ; physiology ; Humans ; Neoplasms ; metabolism ; pathology ; therapy ; Proteolysis ; Signal Transduction

The bone marrow microenvironment composed of bone marrow cell, their secreted cytokines and extra-cellular medium (ECM), plays an important role in the process of hematopoiesis, hematonosis, apoptosis of malignant blood cells. In this review, the mechanisms for the protection of the leukemiic cells from the drug-induced apoptosis by bone marrow stromal cells and the related progress were summarized.
Apoptosis ; Apoptosis Regulatory Proteins ; metabolism ; Bone Marrow Cells ; metabolism ; pathology ; Drug Resistance, Neoplasm ; Humans ; Leukemia ; metabolism ; pathology ; Proto-Oncogene Proteins c-bcl-2 ; metabolism ; Stromal Cells ; metabolism ; pathology

OBJECTIVETo investigate the expressions of survivin and GRIM-19 in prostatic cancer tissue and their clinical implications.

METHODSWe detected the expressions of survivin and GRIM-19 in the tissues of normal prostate (NP), benign prostate hyperplasia (BPH) and prostate cancer (PCa) using immunohistochemical staining, RT-PCR and Western blot, and processed the data by SPSS12.

RESULTSThe positive rates of survivin expression were 6.25% , 18.18% and 90.62% in NP, BPH and PCa (P < 0.01), while those of GRIM-19 were 87.50%, 81.82% and 9.37% , respectively (P < 0.01). Semiquantitative RT-PCR and immunohistochemical staining showed that both survivin mRNA and survivin expressions were highly positive in PCa but negative in NP and BPH. Western blot exhibited that the survivin protein was expressed strongly in PCa but weakly in NP and BPH, while the GRIM-19 protein was expressed just contrariwise (P < 0.01).

CONCLUSIONThe expressions of survivin and GRIM-19 may be closely correlated with the pathogenesis of prostate cancer.

Apoptosis Regulatory Proteins ; metabolism ; Case-Control Studies ; Humans ; Inhibitor of Apoptosis Proteins ; metabolism ; Male ; NADH, NADPH Oxidoreductases ; metabolism ; Prostate ; metabolism ; pathology ; Prostatic Neoplasms ; metabolism ; pathology

Atherosclerosis is a chronic, inflammatory disorder characterized by the deposition of excess lipids in the arterial intima. The formation of macrophage-derived foam cells in a plaque is a hallmark of the development of atherosclerosis. Lipid homeostasis, especially cholesterol homeostasis, plays a crucial role during the formation of foam cells. Recently, lipid droplet-associated proteins, including PAT and CIDE family proteins, have been shown to control the development of atherosclerosis by regulating the formation, growth, stabilization and functions of lipid droplets in macrophage-derived foam cells. This review focuses on the potential mechanisms of formation of macrophage-derived foam cells in atherosclerosis with particular emphasis on the role of lipid homeostasis and lipid droplet-associated proteins. Understanding the process of foam cell formation will aid in the future discovery of novel therapeutic interventions for atherosclerosis.
Acyltransferases ; metabolism ; Apoptosis Regulatory Proteins ; metabolism ; Atherosclerosis ; metabolism ; pathology ; Cholesterol ; metabolism ; Foam Cells ; cytology ; metabolism ; Humans ; Lipid Metabolism ; physiology ; Macrophages ; cytology ; immunology ; Membrane Proteins ; metabolism ; Perilipin-2 ; Peroxisome Proliferator-Activated Receptors ; metabolism ; Sterol Regulatory Element Binding Proteins ; metabolism