Gene/Protein Disease Symptom Drug Enzyme Compound
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Query: UNIPROT:P08758 (annexin V)
 9,383 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

Ascertaining the upstream regulatory mechanisms of hyperthermia-induced apoptosis is important to understand the role of hyperthermia in combined modality cancer therapy. Accordingly, we investigated whether (i) hyperthermia-induced apoptosis is mediated through the nitric oxide (NO) signaling pathway and (ii) inhibition of post-translational modification of IkappaBalpha and down regulation of NFkappaB-DNA binding activity is an intermediate step in NO-dependent apoptosis in MCF-7 breast cancer cells. For hyperthermia treatment, the cells were exposed to 43 degrees C. Intracellular NO levels measured by the fluorescent intensity of DAF-2A and iNOS expression by immunobloting revealed an increased level of iNOS dependent NO production after 43 degrees C. Apoptosis measured by Annexin V expression and cell survival by clonogenic assay showed a 20% increase in apoptosis after 43 degrees C treatments. EMSA analysis showed a dose-dependent inhibition of NFkappaB-DNA binding activity. The hyperthermia-mediated inhibition of NFkappaB was persistent even after 48 h. Inhibition of NO by L-NAME rescued the NFkappaB-DNA binding activity and inhibits heat-induced apoptosis. Similarly, over-expression of NFkappaB by transient transfection inhibits heat-induced apoptosis. These results demonstrate that apoptosis upon hyperthermia exposure of MCF-7 cells is regulated by NO-mediated suppression of NFkappaB.
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PMID:Nitric oxide-mediated inhibition of NFkappaB regulates hyperthermia-induced apoptosis. 1920 36

Amonafide, a naphthalimide derivative, although selected for exploratory clinical trials for its potent anticancer activity, has long been challenged by its unpredictable side effects. In the present study, a novel amonafide analogue, M(2)-A 2-(2-(dimethylamino)ethyl)-6-(thiophene-2-ylmethylamino)-1H-benzo[de]isoquinoline-1,3(2H)-dione was ascribed to its potent effects on topoisomerase IIalpha. Moreover, our investigation indicates that M(2)-A induces G(2)/M phase growth arrest through inhibiting PI3K/Akt pathway. M(2)-A inhibits proliferation of HeLa, HL60, HCT-8, A375, MCF-7 and MRC-5 cells, especially inhibits proliferation of HL60 with an IC(50) value of 18.86 microM. M(2)-A can not only induce DNA fragmentation, but also enhance Annexin V-FITC binding of the cells. On the one hand the expression levels of protein Cyclin B1, Cdk1 changed in response to M(2)-A treatment in HL60 cells. On the other hand we observed the inhibition of NF-kappaB nuclear translocation, up-regulation of Bax and down-regulation of Bcl-2, the caspase -3, -9 activity increase in HL60 cells after treated with M(2)-A, which indicated that the mitochondrial pathway was involved in the apoptosis signal pathway. Our results showed that the phosphorylation of p85/PI3K and Akt decreased following M(2)-A treatment. In summary, M(2)-A displayed a significant anti-tumor effect through cell cycle arrest and apoptotic induction in HL60 cells, which suggested that M(2)-A might have therapeutic potential against leukaemia.
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PMID:M(2)-A induces apoptosis and G(2)-M arrest via inhibiting PI3K/Akt pathway in HL60 cells. 1943 48

We have recently reported that cytostatic concentrations of the microsomal antiestrogen-binding site (AEBS) ligands, such as PBPE (N-pyrrolidino-(phenylmethyphenoxy)-ethanamine,HCl) and tamoxifen, induced differentiation characteristics in breast cancer cells through the accumulation of post-lanosterol intermediates of cholesterol biosynthesis. We show here that exposure of MCF-7 (human breast adenocarcinoma cell line) cells to higher concentrations of AEBS ligands triggered active cell death and macroautophagy. Apoptosis was characterized by Annexin V binding, chromatin condensation, DNA laddering and disruption of the mitochondrial functions. We determined that cell death was sterol- and reactive oxygen species-dependent and was prevented by the antioxidant vitamin E. Macroautophagy was characterized by the accumulation of autophagic vacuoles, an increase in the expression of Beclin-1 and the stimulation of autophagic flux. We established that macroautophagy was sterol- and Beclin-1-dependent and was associated with cell survival rather than with cytotoxicity, as blockage of macroautophagy sensitized cells to AEBS ligands. These results show that the accumulation of sterols by AEBS ligands in MCF-7 cells induces apoptosis and macroautophagy. Collectively, these data support a therapeutic potential for selective AEBS ligands in breast cancer management and shows a mechanism that explains the induction of autophagy in MCF-7 cells by tamoxifen and other selective estrogen receptor modulators.
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PMID:Ligands of the antiestrogen-binding site induce active cell death and autophagy in human breast cancer cells through the modulation of cholesterol metabolism. 1952 24

Sutherlandia frutescens is a South African herb traditionally used for internal cancers, diabetes, a variety of inflammatory conditions and recently to improve the overall health in cancer and HIV/AIDS patients. The in vitro effects of S. frutescens extracts were evaluated on cell numbers, morphology, cell cycle progression and cell death. Dose-dependent studies (2-10 mg/ml) revealed a decrease in malignant cell numbers when compared to their controls. S. frutescens extracts (10 mg/ml) decreased cell growth in a statistically significantly manner to 26% and 49% (P<0.001) in human breast adenocarcinoma (MCF-7) and human non-tumorigenic epithelial mammary gland cells (MCF-12A) respectively after 72 h of exposure. Cell density was significantly compromised and hypercondensed chromatin, cytoplasmic shrinking, membrane blebbing and apoptotic bodies were more pronounced in the MCF-7 cell line. Both S. frutescens-treated cell lines exhibited and increased tendency for acridine orange staining, suggesting increased lysosomal and/or autophagy activity. Flow cytometry showed an increase in the sub G(1) apoptotic fraction and an S phase arrest in both the 5 mg/ml and 10 mg/ml S. frutescens-treated cells. S. frutescens induced an increase in apoptosis in both cell lines as detected by Annexin V and propidium iodide flow cytometric measurement. At 10 mg/ml, late stages of apoptosis were more prominent in MCF-7 S. frutescens-treated cells when compared to the MCF-12A cells. Transmission electron microscopy revealed hallmarks of increased vacuolarization and hypercondensed chromatin, suggesting autophagic and apoptotic processes. The preliminary study demonstrates that S. frutescens water extracts exert a differential action mechanism in non-tumorigenic MCF-12A cells when compared to tumorigenic MCF-7 cells, warranting future studies on this multi-purpose medicinal plant in southern Africa.
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PMID:In vitro effects of Sutherlandia frutescens water extracts on cell numbers, morphology, cell cycle progression and cell death in a tumorigenic and a non-tumorigenic epithelial breast cell line. 1952 21

To investigate the effects of PA-MSHA (Pseudomonas aeruginosa-mannose sensitive hemagglutinin) on inhibiting proliferation of breast cancer cell lines and to explore its mechanisms of action in human breast cancer cells. MCF-10A, MCF-7, MDA-MB-468, and MDA-MB-231HM cells were treated with PA-MSHA or PA (Heat-killed P. aeruginosa) at different concentrations and different times. Changes of cell super-microstructure were observed by transmission electron microscopy. Cell cycle distribution and apoptosis induced by PA-MSHA were measured by flow cytometry (FCM) with PI staining, ANNEXIN V-FITC staining and Hoechst33258 staining under fluorescence microscopy. Western blot was used to evaluate the expression level of apoptosis-related molecules. A time-dependent and concentration-dependent cytotoxic effect of PA-MSHA was observed in MDA-MB-468 and MDA-MB-231HM cells but not in MCF-10A or MCF-7 cells. The advent of PA-MSHA changed cell morphology, that is to say, increases in autophagosomes, and vacuoles in the cytoplasm could also be observed. FCM with PI staining, ANNEXIN V-FITC and Hoechst33258 staining showed that the different concentrations of PA-MSHA could all induce the apoptosis and G(0)-G(1) cell cycle arrest of breast cancer cells. Cleaved caspase 3, 8, 9, and Fas protein expression levels were strongly associated with an increase in apoptosis of the breast cancer cells. There was a direct relationship with increased concentrations of PA-MSHA but not of PA. Completely different from PA, PA-MSHA may impart antiproliferative effects against breast cancer cells by inducing apoptosis mediated by at least a death receptor-related cell apoptosis signal pathway, and affecting the cell cycle regulation machinery.
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PMID:PA-MSHA inhibits proliferation and induces apoptosis through the up-regulation and activation of caspases in the human breast cancer cell lines. 1956 67

A series of novel naphthalimide derivatives with flexible alkyl/aryl moieties were designed and synthesized. Their antitumor activities were evaluated against HeLa, A549, P388, HL-60, MCF-7, HCT-8 and A375 cancer cell lines in vitro. The preliminary results showed that most of the derivatives had comparable antitumor activities over Amonafide with the IC(50) values of 10(-6) to 10(-5)M. More importantly, flow cytometric analysis indicated that the derivatives could effectively induce G(2)/M arrest and progress to apoptosis in HL-60 cell line after double staining with annexin V-FITC and propidium iodide. The present work provided a novel class of naphthalimide-based derivatives with potent apoptosis-inducing and antitumor activities for further optimization.
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PMID:Novel naphthalimide derivatives as potential apoptosis-inducing agents: design, synthesis and biological evaluation. 1964 13

In recent times self-assembled micellar nanoparticles have been successfully employed in tissue engineering for targeted drug delivery applications. In this review, silk sericin protein from non-mulberry Antheraea mylitta tropical tasar silk cocoons was blended with pluronic F-127 and F-87 in the presence of solvents to achieve self-assembled micellar nanostructures capable of carrying both hydrophilic (FITC-inulin) and hydrophobic (anticancer drug paclitaxel) drugs. The fabricated nanoparticles were subsequently characterized for their size distribution, drug loading capability, cellular uptake and cytotoxicity. Nanoparticle sizes ranged between 100 and 110 nm in diameter as confirmed by dynamic light scattering. Rapid uptake of these particles into cells was observed in in vitro cellular uptake studies using breast cancer MCF-7 cells. In vitro cytotoxicity assay using paclitaxel-loaded nanoparticles against breast cancer cells showed promising results comparable to free paclitaxel drugs. Drug-encapsulated nanoparticle-induced apoptosis in MCF-7 cells was confirmed by FACS and confocal microscopic studies using Annexin V staining. Up-regulation of pro-apoptotic protein Bax, down-regulation of anti-apoptotic protein Bcl-2 and cleavage of regulatory protein PARP through Western blot analysis suggested further drug-induced apoptosis in cells. This study projects silk sericin protein as an alternative natural biomaterial for fabrication of self-assembled nanoparticles in the presence of poloxamer for successful delivery of both hydrophobic and hydrophilic drugs to target sites.
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PMID:Self-assembled silk sericin/poloxamer nanoparticles as nanocarriers of hydrophobic and hydrophilic drugs for targeted delivery. 1967 63

The aim of the present study was to determine the effect of the combination of tumor necrosis factor-related apoptosis-inducing ligand (TRAIL) and adriamycin (ADM) on the human breast cancer cell line MCF-7 and to identify potential mechanisms of apoptosis. Cell viability was analyzed by the MTT assay and the synergistic effect was assessed by the Webb coefficient. Apoptosis was quantified using the annexin V-FITC and propidium iodide staining flow cytometry. The mRNA expression of TRAIL receptors was measured by RT-PCR. Changes in the quantities of Bax and caspase-9 proteins were determined by Western blot. MCF-7 cells were relatively resistant to TRAIL (IC50 >10 microg/mL), while MCF-7 cells were sensitive to ADM (IC50 <10 microg/mL). A subtoxic concentration of ADM (0.5 microg/mL) combined with 0.1, 1, or 10 microg/mL TRAIL had a synergistic cytotoxic effect on MCF-7 cells, which was more marked with the combination of TRAIL (0.1 microg/mL) and ADM (0.5 microg/mL). In addition, the combined treatment with TRAIL and ADM significantly increased cell apoptosis from 9.8% (TRAIL) or 17% (ADM) to 38.7%, resulting in a synergistic apoptotic effect, which is proposed to be mediated by up-regulation of DR4 and DR5 mRNA expression and increased expression of Bax and caspase-9 proteins. These results suggest that the combination of TRAIL and ADM might be a promising therapy for breast cancer.
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PMID:Synergistic antitumor effect of TRAIL and adriamycin on the human breast cancer cell line MCF-7. 1973 90

Tumor necrosis factor-related apoptosis-inducing ligand (TRAIL) is a promising candidate for cancer therapeutics due to its ability to induce apoptosis selectively in cancer cells. However, sensitivity of cancer cells for induction of apoptosis by TRAIL varies considerably. Therefore, it is important to develop agents that overcome this resistance. We show, for the first time, that eupatolide, the sesquiterpene lactone isolated from the medicinal plant Inula britannica, sensitizes human breast cancer cells to TRAIL-induced apoptosis. Treatment with TRAIL in combination with subtoxic concentrations of eupatolide enhanced the TRAIL-induced cytotoxicity in MCF-7, MDA-MB-231 and MDA-MB-453 breast cancer cells, whereas each reagent alone slightly induced cell death. The combination induced sub-G1 phase DNA content and annexin V-staining in MCF-7 cells, which are major features of apoptosis. Apoptotic characteristics induced by the combined treatment were significantly inhibited by a pan-caspase inhibitor. The sensitization to TRAIL-induced apoptosis was accompanied by the activation of caspase-8 and was concomitant with Bid and poly(ADP-ribose) polymerase (PARP) cleavage. Treatment of eupatolide alone significantly down-regulated the expression of cellular FLICE inhibitory protein (c-FLIP) in MCF-7 cells. Furthermore, enforced expression of c-FLIP significantly attenuated the apoptosis induced by this combination in MCF-7 cells, suggesting a key role for c-FLIP down-regulation in these events. We also observed that euaptolide inhibited AKT phosphorylation in a dose- and time-dependent manner. Moreover, inhibition of Akt by LY294002, a specific PI3K inhibitor, down-regulated c-FLIP expression in MCF-7 cells. Taken together, these results indicate that eupatolide could augment TRAIL-induced apoptosis in human breast cancer cells by down-regulating c-FLIP expression through the inhibition of AKT phosphorylation and be a valuable compound to overcome TRAIL resistance in breast cancer cells.
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PMID:The sesquiterpene lactone eupatolide sensitizes breast cancer cells to TRAIL through down-regulation of c-FLIP expression. 1995 87

Four novel dinuclear platinum(II) complexes of formula [Pt2L4(berenil)2]Cl4 (Pt1-Pt4) where L is piperazine (Pt1), 4-picoline (Pt2), 3-picoline (Pt3) or isopropylamine (Pt4) were compared to cisplatin in respect to collagen biosynthesis, beta1- integrin receptor, IGF-I receptor, phosphorylated MAP-kinases (ERK1/ERK2 and p38), phosphorylated Akt kinase expression and appearance of apoptosis in MCF-7 breast cancer cells. It was found that Pt1-Pt4 were more active inhibitor of collagen biosynthesis than cisplatin. The expression of IGF-I and beta1 integrin receptor, as well as phosphorylated MAPK, (ERK1 and ERK2 and p38) was significantly increased in cells incubated for 24 h with 20 muM Pt1-Pt4 compared to the control, not treated cells. The phenomenon was related to the increase expresion of NFkappaB by Pt1-Pt4 as shown by Western immunoblot analysis. Experiments made with annexin V-FITC and detection of apoptosis by a fluorescent microscopy assay revealed that novel dinuclear platinum(II) complexes (Pt1-Pt4) inhibited the proliferation of MCF-7 breast cancer cells by increasing the number of apoptotic and necrotic cells.
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PMID:Novel dinuclear platinum(II) complexes targets NFkappaB signaling pathway to induce apoptosis and inhibit metabolism of MCF-7 breast cancer cells. 2006 86


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