BACKGROUND: The capacity of photosensitizing chemicals with ultraviolet A light (UVA) to induce apoptosis is one of the methods to assess their phototoxic and potentially photoallergic properties, since apoptotic cells may be easily presented by antigen-presenting cells. OBJECTIVES: We examined the photoaggravated ability to induce keratinocyte apoptosis of various chemicals ...

Neuroblastoma is the most common extracranial solid tumor in children causing death at pre-school age, as no cure has yet been developed. We investigated the proteolytic mechanisms for apoptosis in human malignant (N-type) neuroblastoma SH-SY5Y cells following exposure to flavonoids such as apigenin (APG), (-)-epigallocatechin (EGC), (-)-epigallocatechin-3-gallate (EGCG) and genistein ...

Costimulation of T cells via CD28 promotes both proliferation and resistance to apoptosis. In this study, we show that the immunosuppressive drug cyclosporin A (CsA) fully reverses resistance to CD95-mediated cell death after TCR/CD28 costimulation or superagonistic anti-CD28 mAb stimulation of primary rat lymph node T cells. This effect correlated ...

Induction of defense response against Karnal bunt (KB)by suppressing the pathogenesis was observed upon exogenous application of jasmonic acid (JA)as evident from decrease in the coefficient of infection and overall response value in both susceptible and resistant varieties of wheat. The ultra-structural changes during disease progression showed the signs of ...

To investigate the effect of polyol pathway on lens epithelial cells apoptosis and the activity of caspase-3 and its reversal by pyruvate in diabetic rats. 220 Wister rats were divided into 3 groups: control group, model group and treatment group. After streptozotocin (STZ) induced cataract, the treatment group received 2% ...

The contribution of different proteolytic systems, in particular calpains and effector caspases, in apoptotic cell death is still controversial. In this paper, we show that during cisplatin-induced apoptosis of human metastatic melanoma cells, calpain activation, as measured in intact cells by two different fluorescent substrates, is an early event, taking ...

Aberrant apoptosis has been associated with the development and therapeutic resistance of cancer. Recent studies suggest that caspase deficiency/downregulation is frequently detected in different cancers. We have previously shown that caspase-3 reconstitution significantly sensitized MCF-7 cells to doxorubicin and etoposide. In contrast to the well established role of caspase-3 as ...

Obesity is biologically characterized at the cellular level by an increase in the number and size of adipocytes differentiated from fibroblastic pre-adipocytes in adipose tissue. In this study, we focused on the relationship between the influence of flavonoids on cell population growth and their antioxidant activity. The results showed that ...

Lysosomal cysteine protease cathepsin B has been reported to play an important role in apoptosis of many different cancer cells, but the regulation of cathepsin B in apoptosis is poorly understood. Human homologue of SETA binding protein 1 (hSB1) was identified to interact with cathepsin B by yeast-two hybrid method, ...

Taxol is an anticancer drug that triggers apoptosis in a wide spectrum of cancers such as ovarian, breast, lung, head and neck, and bladder carcinoma by both caspase-dependent and -independent apoptosis mechanisms. However, the exact signaling pathways involved in taxol-induced apoptosis strongly depend on the cellular background and they are ...

alpha-1 Antitrypsin (A1AT) is an abundant circulating serpin with a postulated function in the lung of potently inhibiting neutrophil-derived proteases. Emphysema attributable to A1AT deficiency led to the concept that a protease/anti-protease imbalance mediates cigarette smoke-induced emphysema. We hypothesized that A1AT has other pathobiological relevant functions in addition to elastase ...

Uncontrolled calcium stress has been linked causally to a variety of neurodegenerative diseases, including ischemia, excitotoxicity and Alzheimer's disease. Thapsigargin, which increases [Ca2+]i, induces apoptotic cell death (chromatin condensation and DNA fragmentation) accompanied by caspase-3 activation in PC12 cells. We examined whether GSK-3 is involved in thapsigargin-induced cell death by ...

Estrogens are developmental regulators of mitochondrial apoptotic pathway in the central nervous system, but little is known about their involvement in cytokine-induced apoptosis. In the present study, we evaluated effects of 17beta-estradiol on pro-inflammatory cytokine- and staurosporine-mediated activation of caspase-3 and LDH-release in primary neuronal/glial cell cultures of mouse hippocampal ...

ABSTRACT Parvovirus B19 persists in multiple tissues and has been implicated in a variety of diseases including acute fulminant liver failure (AFLF). Despite multiple reports demonstrating the presence of B19 DNA in liver tissues from patients with AFLF, the causal relationship of B19 infection to liver failure is not yet ...

Bee venom (BV) has been known to inhibit proliferation and induce apoptosis in cancer cells. However, the molecular mechanisms involved in BV-induced apoptosis are still uncharacterized in human leukemic cells. In the present study, we report that BV induces apoptosis in leukemic U937 cells through downregulation of ERK and Akt ...

Camptothecin and doxorubicin belong to a family of anticancer drugs that exert cytotoxic effects by triggering apoptosis in various cell types. However there have only been few investigations showing that matricellular proteins like thrombospondin-1 (TSP-1) could be involved in the underlying mechanism of this cytotoxicity. In this report, using Hoechst ...

Anthrax toxin protective antigen (PA) binds cell surface receptors (e.g. ANTXR1,2), forms heptameric pores, and translocates lethal factor (LF) or oedema factor (OF) into the cytoplasm of mammalian cells. In the current study, we sought to determine how receptor levels influence these events, by examining PA heptamer stability and related ...

Trichosanthin (TCS), a type I ribosome-inactivating protein, induces cell death in various cell types including several tumor cell lines. However, the mechanism remains largely uncharacterized. In this study, we investigated the possible mechanism underlying its cytotoxicity by using human chronic myeloid leukemia cell line K562. We found that TCS induced ...

BACKGROUND: Cardioplegic arrest (CA) using cold blood cardioplegia (CBC) has been reported to reduce ischemia-reperfusion (IR)-induced myocardial injury via apoptosis. We studied key apoptotic mediators via the caspase-dependent and intrinsic pathways as well as poly(ADP)-ribosylating protein (PARP) activity in myocardial and peripheral tissues after CA and cardiopulmonary bypass (CBP). METHODS ...

Sjögren's syndrome (SS) is an autoimmune rheumatic disease that targets salivary and lachrymal glands, characterized by a high concentration of serum autoantibodies directed against nuclear and cytoplasmic antigens. It is known that autoantibodies can enter viable cells and this phenomenon has functional consequences including activation of apoptotic process. The objective ...

Group B Streptococcus (GBS) has developed several strategies to evade immune defenses. We show that GBS induces macrophage (Mphi) membrane permeability defects and apoptosis, prevented by inhibition of calcium influx but not caspases. We analyze the molecular mechanisms of GBS-induced murine Mphi apoptosis. GBS causes a massive intracellular calcium increase, ...

Cytotoxic T cells and NK cells will acquire features of apoptosis when exposed to oxygen radicals, but the molecular mechanisms underlying this phenomenon are incompletely understood. We have investigated the role of two enzyme systems responsible for execution of cell death, caspases and the poly(ADP-ribose) polymerase (PARP). We report that ...

Enzastaurin displays pro-apoptotic properties against a spectrum of malignancies and is currently being investigated in clinical trials. We have investigated the effects of enzastaurin on the viability of the cutaneous T-cell lymphoma cell lines HuT-78 and HH by using 3-(4,5-dimethylthiazol-2-yl)-5(3-carboxymethoxyphenyl)-2-(4-sulfophenyl)-2H-tetrazolium assay, cell cycle analysis, propidium iodide and annexin-V staining, and ...

Virus infection may induce host cell death by apoptosis, but some DNA viruses are capable of preventing this process. RNA viruses were thought not to display anti-apoptotic activities, as their spread appears to benefit from a rapid induction of cell death. Here, we report an antiapoptotic activity in the Picornavirus ...

The nephrotoxic metal cadmium at micromolar concentrations induces apoptosis of rat kidney proximal tubule (PT) cells within 3-6 h of exposure. The underlying cell death pathways remain poorly defined. Using Hoechst 33342/ethidium bromide nuclear staining and 3-(4,5-dimethyl-2-thiazolyl)-2,5-diphenyl-2H-tetrazolium bromide (MTT) cell death assays, 10-50 microM cadmium induced apoptosis of immortalized rat ...

The study examined the effects of various progesterone and mifepristone concentrations on the proliferation and apoptosis of the human ovarian cancer cell line, OVCAR-3. OVCAR-3 cells were incubated with progesterone and mifepristone at concentrations ranging from 10(-3) to 10(-9) M. Proliferation and apoptosis were studied by means of inverted optical ...

The pathogenesis of severe acute respiratory syndrome-associated coronavirus (SARS-CoV) is an important issue for the treatment and prevention of severe acute respiratory syndrome. Recently, SARS-CoV has been demonstrated to induce cell apoptosis in Vero-E6 cells. The possible role of SARS-CoV 3C-like protease (3CLpro) in virus-induced apoptosis is characterized in this ...

The anti-cancer effects of cytosine arabinoside (ARA-C) are well known. However, effects on nonmalignant cells have not been elucidated and may be important to understanding treatment-related toxicity. The purpose of this study was to examine the effect of ARA-C on nondividing vascular endothelial cells. The objectives were to determine the ...

In this study, the effects of melatonin on MPP+ -treated cerebellar granule neurons (CGNs) in culture were investigated. Results showed that MPP+ treatment significantly decreased cell viability and increased the apoptotic cell population at 24 and 48 hr. Calpain and caspase-3 activation was also determined, with results showing a strong ...

The anti-cancer effects and possible mechanisms of the freshwater clam (Corbicula fluminea Muller) and its active compounds (FME) on cell viability in human leukemia HL-60 cells were investigated. This study demonstrated that FME was able to inhibit cell proliferation in a concentration- and time-dependent manner. Treatment with FME caused induction ...

AIM: To study in vitro the molecular mechanism of apoptosis caused by beta-lapachone, a quinone obtained from the bark of the lapacho tree (Tabebuia avellanedae). MATERIALS AND METHODS: The study was carried out on human bladder carcinoma T24 cell line. Determination of cell viability was done using trypan blue exclusion ...

Multiple myeloma (MM) is a plasma cell malignancy that claims thousands of lives each year and has considerable morbidity. The disease remains incurable despite recent advances in the understanding of the disease biology and the introduction of more effective drugs is needed. This study evaluated the anti-MM activity of 3-(7-fluoro-4H-quinazolin-3-yl)-piperidine-2,6-dione, ...

Phospholipase A2 (PLA2) is an esterase that cleaves the sn-2 ester bond in glycerophospholipids, thereby releasing free fatty acids and lysophospholipids. In addition to the apoptotic activity of cytosolic PLA2 and Ca2+-independent PLA2, recent studies showed that secretory PLA2 (sPLA2) also play a role in apoptosis. However, the details of ...

Apoptosis can be mediated by different mechanisms. There is growing evidence that different proteolytic enzymes are involved in the regulation of apoptosis. Cathepsins are proteases which, under physiologic conditions, are localized intralysosomally. In response to certain signals they are released from the lysosomes into the cytoplasm where they trigger apoptotic ...

Cardiomyocytic apoptosis occurs after cardiopulmonary bypass (CPB) despite the use of perfusion techniques and cardioplegic solutions. Reactive oxygen species (ROS) cause single-strand DNA breaks and activate nuclear poly(ADP-ribose) polymerase (PARP), which leads to cellular damage. Therefore, the inhibition of PARP might protect cardiomyocytes from oxidative injuries. In this study, experiments ...

Enterovirus 70 (EV70) is the major etiological agent of acute hemorrhagic conjunctivitis (AHC). EV70 m.o.i.- (multiplicity of infection) and time-dependently induced apoptosis in human Chang's conjunctival (HCC) cells. UV- or heat-inactivated EV70 did not induce apoptosis. EV70-induced apoptosis was inhibited by cycloheximide and methoxysuccinyl-Ala-Ala-Pro-Val-chloromethylketone (MPCMK), but not actinomycin D and ...

6-Hydroxydopamine (6-OHDA) is a selective neurotoxin used to induce apoptosis in catecholamine-containing neurons. Although biochemical products and reactive oxygen species (ROS) of 6-OHDA have been well documented, the activation of cellular pathways following exposure are not well understood. Apoptosis in PC12 (Pheochromocytoma) cells was induced by 6-OHDA in a dose ...

Antrodia camphorata (A. camphorata) is well known in Taiwan as a traditional Chinese medicine, and it has been shown to exhibit antioxidant and anticancer effects. In this study, therefore, its ability to induce apoptosis in cultured MCF-7 breast cancer cells was studied. Treatment of the MCF-7 cells with a variety ...

Matrine, a low toxic alkaloid purified from the Chinese herb Kushen, has been reported to induce apoptosis in leukemia K562 cells. In this study, the mechanism underling this apoptotic event was investigated. Treatment of K562 cells with matrine resulted in inhibition of cell survival more significantly than treatment of non-cancer ...

We evaluated the cytotoxic and apoptotic effects of two purine nucleoside analogues, acyclovir (ACV) and ganciclovir (GCV), on lymphoma cells stably harboring Kaposi's sarcoma-associated herpesvirus (KSHV). Colorimetric caspase assay, flow cytometry, and immunoblotting with antibodies against apoptosis-related molecules revealed that GCV has cytotoxic activity toward KSHV-infected primary effusion lymphoma cells, ...

PURPOSE: Cannabinoids have been associated with tumor regression and apoptosis of cancer cells. Recently, we have shown that R(+)-methanandamide (R(+)-MA) induces apoptosis of H4 human neuroglioma cells via a mechanism involving de novo expression of the cyclooxygenase-2 (COX-2) enzyme. The present study investigated a possible involvement of a mitochondrial-driven pathway ...

The DNA topoisomerase inhibitor beta-lapachone is a quinone obtained from the bark of the lapacho tree (Tabebuia avellanedae) in South America. It has been reported to possess a wide range of pharmacological properties, and is a promising cancer chemopreventive agent. In this study, the effects of beta-lapachone on the growth ...

In this study, the effect of (Boc-Lys (Boc)-Arg-Asp-Ser (tBu)-OtBu), a tetrapeptide derivative (PEP1261) was examined for antiproliferative potency and apoptotic induction. Synovial fibroblasts were isolated from collagen-induced arthritic (CIA) rats and exposed to peptides viz., PEP1261, and parental peptides (KRDS and RGDS). Viability of the cells decreased in the presence ...

BACKGROUND: Glutamate, a major excitatory amino acid neurotransmitter, causes apoptotic neuronal cell death at high concentrations. Our previous studies have shown that depending on the neuronal cell type, glutamate-induced apoptotic cell death was associated with regulation of genes such as Bcl-2, Bax, and/or caspase-3 and mitochondrial cytochrome c. To further ...

Triptolide is a compound extracted from the Chinese herb Tripterygium wilfordii Hook. f. Triptolide has potent anticancer activity. However, the mechanisms by which triptolide exerts its anticancer activities remain unclear. To explore the molecular mechanisms involved in the anticancer activity of triptolide, we have examined the effect of triptolide on ...

Increasing evidence suggests that lysosomal cysteine proteases cathepsins contribute to the progression of cell apoptosis. Here we found that apoptosis of ovarian cancer cells OV-90 triggered by TNF was cathepsin B-depended. Two cathepsin B binding proteins, bikunin and TSRC1, were identified by yeast two-hybrid method and the interactions were confirmed ...

We investigated the mechanism of the pan-caspase inhibitor z-VAD-fmk's augmentation of TNFalpha-induced L929 cell death and found this mechanism differs from that of TNFalpha-induced L929 cell death. In the presence of 20 ng/ml TNFalpha, z-VAD-fmk initiated apoptosis and necrosis in the majority of L929 cells as measured by an agarose ...

We evaluated the antitumor activity of tocotrienol (T3) on human hepatoma Hep3B cells. At first, we examined the effect of T3 on the proliferation of human hepatoma Hep3B cells and found that gamma-T3 inhibited cell proliferation at lower concentrations and shorter treatment times than alpha-T3. Then, we examined the effect ...

BACKGROUND: Cyclo(Phe-Pro) has been shown to inhibit cancer cell growth and induce apoptosis in HT-29 colon cancer cells. MATERIALS AND METHODS: The molecular mechanisms mediating cyclo(Phe-Pro)-induced apoptosis in HT-29 cells were investigated. Cells were treated with 5 mM or 10 mM cyclo(Phe-Pro) for varying times. Immunoblot analysis was used to ...

We investigated the effects of ircinin-1, a lipid compound (a C25 sesterterpene tetronic acid) isolated from marine sponges (Sarcotragus sp.), on the modulation of cell cycle and induction of apoptosis in SK-MEL-2 human skin cancer cells (mutant p53). Ircinin-1 treatment on SK-MEL-2 cells resulted in a dose-dependent inhibition of cell ...