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Apoptotic Effects (apoptotic + effects)
Selected AbstractsPolyprenylated Xanthones from Garcinia lancilimba Showing Apoptotic Effects against HeLa-C3 CellsCHEMISTRY & BIODIVERSITY, Issue 12 2008Quan-Bing Han Abstract Three new prenylated xanthones, 1,3, along with ten known compounds, were isolated from the stem bark of Garcinia lancilimba. Their structures were elucidated by extensive spectroscopic analysis, including 1D- and 2D-NMR spectra, as well as HR-MS experiments. Some of these compounds showed apoptotic effects or growth-inhibition effects against HeLa cells expressing a caspase sensor protein. [source] Comparison of the aggregation properties, secondary structure and apoptotic effects of wild-type, Flemish and Dutch N-terminally truncated amyloid , peptidesEUROPEAN JOURNAL OF NEUROSCIENCE, Issue 11 2001N. Demeester Abstract The Dutch (E22Q) and Flemish (A21G) mutations in the ,APP region of the amyloid precursor protein (APP) are associated with familial forms of Alzheimer dementia. However, patients with these mutations express substantially different clinical phenotypes. Therefore, secondary structure and cytotoxic effects of the three A,(12,42) variants [wild-type (WT), Dutch and Flemish] were tested. At a concentration of 5 µm the aggregation of these peptides followed the order: A,(1,42) WT > A,(12,42) WT > A,(12,42) Flemish >,A,(12,42) Dutch. The stability of the secondary structure of these peptides upon decreasing the trifluoroethanol (TFE) concentration in the buffer was followed by circular dichroism measurements. WT peptides progressively lost their ,-helical structure; this change occurred faster for both the Flemish and Dutch peptides, and at higher percentages of TFE in the buffer, and was accompanied by an increase in ,-sheet and random coil content. Apoptosis was induced in neuronal cells by the A,(12,42) WT and Flemish peptides at concentrations as low as 1,5 µm, as evidenced by propidium iodide (PI) staining, DNA laddering and caspase-3 activity measurements. Even when longer incubation times and higher peptide concentrations were applied the N-truncated Dutch peptide did not induce apoptosis. Apoptosis induced by the full length A,(1,42) peptide was weaker than that induced by its N-truncated variant. These data suggest that N-truncation enhanced the cytotoxic effects of A, WT and Flemish peptides, which may play a role in the accelerated progression of dementia. [source] Phospholipase stimulates lipogenesis in SZ95 sebocytesEXPERIMENTAL DERMATOLOGY, Issue 7 2008S. Schagen Introduction:, With progressing ageing human sebocytes reduce lipid production. However, the influence of certain aging mechanisms on sebaceous lipid synthesis as well as ways to influence the latter is not fully identified. Certain lipids act as ligands of nuclear receptors such as PPAR. Phospholipase (PLA2) catalyzes the hydrolysis of the sn-2 fatty acyl bond of phospholipids to yield free fatty acid and lysophospholipid. It has been hypothesized that PPAR may be activated by hydrolysis products of phospholipids and also by eicosanoids obtained through PLA2 activity. Materials and Methods:, A method to quantify sebaceous lipid synthesis of SZ95 sebocytes in vitro was established and the cells were treated by snake venom Bothrops moojeni gel filtration fractions (Botmo GF). Botmo GF fractions were further purified by RP-HPLC, and a fraction with PLA2 activity (Botmo GF11-117) and a fraction without enzymatic activity (Botmo GF11-101) were identified and additionally tested. Results:, Botmo GF fractions increased lipogenesis in SZ95 sebocytes without inducing apparent toxic or apoptotic effects. Botmo GF11-101 (1 ,g/ml) enhanced neutral lipid synthesis by up to 170% and polar lipid synthesis by up to 120%. The enzymatically active PLA2 Botmo GF11-117 (1 ,g/ml) increased synthesis of neutral lipids by up to 200%, and polar lipids by up to 120% compared to untreated SZ95 sebocytes. Conclusion:, PLA2 activation or suppression could be important for human sebaceous lipogenesis. PLA2 modifiers may be attractive for skin lipid research and pharmacological/cosmetic products. [source] Linear relationship between Wnt activity levels and apoptosis in colorectal carcinoma cells exposed to butyrateINTERNATIONAL JOURNAL OF CANCER, Issue 4 2004Darina L. Lazarova Abstract We have reported that butyrate, a fatty acid produced by dietary fiber that induces cell cycle arrest, differentiation and/or apoptosis in colorectal carcinoma (CRC) cells in vitro, modulates Wnt activity in 2 CRC cell lines (Bordonaro et al., Int. J. Cancer, 2002; 97:42,51). Our study determines how changes in the levels of Wnt activity induced by butyrate relate to the effects of butyrate on apoptosis, cell cycle arrest and differentiation of CRC cells. In 10 human CRC cell lines a direct relationship was shown between apoptosis and butyrate-induced increase in Wnt activity, as well as between suppressed clonal growth and increased Wnt activity. No correlation existed between butyrate-induced increase in Wnt activity and differentiation. The direct relationship between apoptosis and Wnt activity was supported by analyses of DLD-1 and HCT-116 cells expressing a dominant negative form of Tcf4, and therefore, with repressed Wnt activity, as well as by measuring the ratio of apoptotic to live cells in flow cytometry-sorted cell fractions with high and low Wnt activity. Novel flow cytometric methodology was utilized to show that butyrate differentially increases the number of cells with Wnt activity in different CRC cell lines. Thus, CRC cell lines in which butyrate upregulated Wnt activity to relatively high levels were most susceptible to the apoptotic effects of butyrate, whereas cell lines in which butyrate modestly modulated Wnt activity were less affected. © 2004 Wiley-Liss, Inc. [source] Mitogenic and Apoptotic Signaling by Carotenoids: Involvement of a Redox MechanismIUBMB LIFE, Issue 1 2001Paola Palozza Abstract The potential for carotenoids to modulate tumor growth is currently under investigation. Although epidemiological studies evidence that a high intake of vegetables, rich in carotenoids, decreases cancer incidence and mortality, clinical trials demonstrate that supplementation of ,-carotene to chronic smokers or to asbestos workers increases the risk for lung cancer. These contradictory findings have renewed interest in elucidating the mechanism of action of carotenoids in biological systems. In this review, we show evidence for mitogenic and apoptotic effects of carotenoids and we support the hypothesis that these molecules may act as anticarcinogens or as procarcinogens through a redox mechanism. In particular, we report demonstrations for the anti-oxidant or pro-oxidant effects of carotenoids in vitro and in vivo, focusing our attention on the relationship existing between cell growth and redox status. [source] Antiproliferative and apoptotic effects of the herbal agent Pygeum africanum on cultured prostate stromal cells from patients with benign prostatic hyperplasia (BPH) ,,THE PROSTATE, Issue 10 2010Maria T. Quiles Abstract BACKGROUND Previous reports show that the herbal agent Pygeum africanum (PA) used to treat benign prostatic hyperplasia (BPH) inhibits proliferation of prostate stromal cells from BPH tissues. To determine underlying mechanisms, we compared proliferative and apoptotic responses to PA between BPH and non-BPH prostate stromal cells with a focus on the specific reaction displayed by stromal cell subsets. An interaction of PA with growth factors and hormones was also investigated. METHODS Primary prostate stromal cells from BPH/LUTS patients undergoing open prostatectomy (n,=,3) and patients without benign prostatic hyperplasia (BPH) undergoing cystectomy (n,=,3) were treated with PA. Cells were characterized by immunofluorescence. Sensitivity to PA was determined using proliferation assays. Apoptosis, transforming growth factor B1 (TGFB1), fibroblast growth factor 2 (FGF2), vimentin, , smooth muscle actin (,SMA), and smoothelin expression were examined after PA treatment. Cell immunophenotype and proliferation were tested after incubating cells with PA plus either FGF2, TGFB1, vascular endothelial growth factor (VEGF), dihydrotestosterone (DHT) or 17,-estradiol (E2). RESULTS Antiproliferative potency and apoptosis induced by PA on stromal cells were increased in BPH versus non-BPH cells. Apoptosis targeted ,SMA+ cells, more abundant in BPH cells. Downregulation of TGFB1 expression was induced by PA. FGF2 increased cells sensitivity to PA. Incubation with other mitogenic factors like VEGF, DHT, and E2 decreased sensitivity to PA. Both TGFB1 and E2 blocked the antiproliferative activity of PA. CONCLUSIONS Results suggest that PA is antiproliferative and apoptotic on proliferative prostate fibroblasts and myofibroblasts but not on smooth muscle cells. Mechanisms of action include TGFB1 downregulation and inhibition of FGF2 specific signaling. Prostate 70: 1044,1053, 2010. © 2010 Wiley-Liss, Inc. [source] Regulation of cell survival by resveratrol involves inhibition of NF,B-regulated gene expression in prostate cancer cellsTHE PROSTATE, Issue 10 2009Dixan A. Benitez Abstract BACKGROUND Polyphenols have been proposed as antitumoral agents. We have shown that resveratrol (RES) induced cell cycle arrest and promoted apoptosis in prostate cancer cells by inhibition of the PI3K pathway. The RES effects on NF,B activity in LNCaP cells (inducible NF,B), and PC-3 cells (constitutive NF,B) are reported. METHODS Cells were treated with 1,150 µM of RES during 36 hr. NF,B subcellular localization was analyzed by western blot and immunofluorescence. I,B, was evaluated by immunoprecipitation followed by Western blot. Specific DNA binding of NF,B was determined by EMSA assays and NF,B-mediated transcriptional activity by transient transfection with a luciferase gene reporter system. RESULTS RES induced a dose-dependent cytoplasmic retention of NF,B mediated by I,B, in PC-3 cells but not in LNCaP. RES-induced inhibition of NF,B specific binding to DNA was more significant in PC-3 cells. NF,B-mediated transcriptional activity induced by EGF and TNF, were inhibited by RES in both cell lines. LY294002 mimicked RES effects on NF,B activity. CONCLUSION Antiproliferative and apoptotic effects of RES on human prostate cancer cells may be mediated by the inhibition of NF,B activity. This mechanism seems to be associated to RES-induced PI3K inhibition. RES could have therapeutic potential for prostate cancer treatment. Prostate 69:1045,1054, 2009. © 2009 Wiley-Liss, Inc. [source] In vitro targeted photodynamic therapy with a pyropheophorbide-a conjugated inhibitor of prostate-specific membrane antigenTHE PROSTATE, Issue 6 2009Tiancheng Liu Abstract BACKGROUND The lack of specific delivery of photosensitizers (PSs), represents a significant limitation of photodynamic therapy (PDT) of cancer. The biomarker prostate-specific membrane antigen (PSMA) has attracted considerable attention as a target for imaging and therapeutic applications for prostate cancer. Although recent efforts have been made to conjugate inhibitors of PSMA with imaging agents, there have been no reports on PS-conjugated PSMA inhibitors for targeted PDT of prostate cancer. The present study focuses on the use of a PSMA inhibitor-conjugate of pyropheophorbide-a (Ppa-conjugate 2) for targeted PDT to achieve apoptosis in PSMA+ LNCaP cells. METHODS Confocal laser scanning microscopy with a combination of nuclear staining and immunofluorescence methods were employed to monitor the specific imaging and PDT-mediated apoptotic effects on PSMA-positive LNCaP and PSMA-negative (PC-3) cells. RESULTS Our results demonstrated that PDT-mediated effects by Ppa-conjugate 2 were specific to LNCaP cells, but not PC-3 cells. Cell permeability was detected as early as 2 hr by HOE33342/PI double staining, becoming more intense by 4 hr. Evidence for the apoptotic caspase cascade being activated was based on the appearance of poly-ADP-ribose polymerase (PARP) p85 fragment. Terminal deoxynucleotidyl transferase dUTP nick end labeling (TUNEL) assay detected DNA fragmentation 16 hr post-PDT, confirming apoptotic events. CONCLUSIONS Cell permeability by HOE33342/PI double staining as well as PARP p85 fragment and TUNEL assays confirm cellular apoptosis in PSMA+ cells when treated with PS-inhibitor conjugate 2 and subsequently irradiated. It is expected that the PSMA targeting small-molecule of this conjugate can serve as a delivery vehicle for PDT and other therapeutic applications for prostate cancer. Prostate 69:585,594, 2009. © 2009 Wiley-Liss, Inc. [source] Apigenin drives the production of reactive oxygen species and initiates a mitochondrial mediated cell death pathway in prostate epithelial cellsTHE PROSTATE, Issue 2 2005Colm Morrissey Abstract BACKGROUND Phytoestrogens may reduce tumorigenesis in prostate cancer. We screened five phytoestrogens for their effect on cell growth and apoptosis in PWR-1E, LNCaP, PC-3, and DU145 prostate epithelial cells in vitro. METHODS We assessed cell number, proliferation, and apoptosis using crystal violet assays, flow cytometric analysis, and TUNEL. Focusing specifically on apigenin we assessed the ability of calpain, serine protease, caspase, estrogen receptor, and ceramide synthase inhibitors to block apigenin induced apoptosis. We also analyzed caspase 3, 7, 8, 9, Bcl-2, Bax, Bid, and cytochrome C by Western analysis, and mitochondrial permeability and reactive oxygen species production by flow cytometry using mitosensorTM and DCFH-DA, respectively. RESULTS Apigenin and silybinin significantly reduced cell number, with apigenin inducing apoptosis in PWR-1E, LNCaP, PC-3, and DU145 cells. The PC-3 and DU145 cells were less susceptible to apigenin induced apoptosis then LNCaP and PWR-1E cells. The induction of apoptosis by apigenin was caspase dependent. Apigenin generated reactive oxygen species, a loss of mitochondrial Bcl-2 expression, mitochondrial permeability, cytochrome C release, and the cleavage of caspase 3, 7, 8, and 9 and the concomitant cleavage of the inhibitor of apoptosis protein, cIAP-2. The overexpression of Bcl-2 in LNCaP B10 cells reduced the apoptotic effects of apigenin. CONCLUSIONS Apigenin induces cell death in prostate epithelial cells using a mitochondrial mediated cell death pathway. Bcl-2 has a role in inhibiting apigenin induced cell death in prostate epithelial cells. © 2004 Wiley-Liss, Inc. [source] Polyprenylated Xanthones from Garcinia lancilimba Showing Apoptotic Effects against HeLa-C3 CellsCHEMISTRY & BIODIVERSITY, Issue 12 2008Quan-Bing Han Abstract Three new prenylated xanthones, 1,3, along with ten known compounds, were isolated from the stem bark of Garcinia lancilimba. Their structures were elucidated by extensive spectroscopic analysis, including 1D- and 2D-NMR spectra, as well as HR-MS experiments. Some of these compounds showed apoptotic effects or growth-inhibition effects against HeLa cells expressing a caspase sensor protein. [source] | |||||||||||||