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

This study was aimed to investigate the changes of silencer of death domains (SODD), survivin, caspase 3, caspase 8 and caspase 9 in the apoptotic process of human leukemia cells induced by chemotherapeutic drugs in order to explore the molecular mechanism of apoptotic modulatory genes and to search for the new target of chemotherapeutic drugs. After Jurkat cells were induced by chemotherapeutic drugs, the translocated phosphatidylserine was labeled with annexin V/PI, and the apoptosis incidence was measured by FCM; The expression changes of SODD, caspase 3, caspase 8 and caspase 9 were determined by Western blot; the changes of survivin mRNA and protein were determined by RT-PCR and immunohistochemistry SABC method respectively. The results indicated that high expressions of SODD and survivin could inhibit apoptotic signaling pathway; VCR down-regulated the function of SODD protein and effectively induced the apoptosis of Jurkat cells in a time-dependent manner and activates caspase 3 through the death receptor-mediated activation of caspase 8, in which caspase 9 and survivin were not degraded. It is concluded that SODD participates in the apoptotic process induced by VCR which induces the Jurkat cell apoptosis by downregulating expression of SODD protein and priming death receptor pathway. In the apoptotic process, the mitochondrion apoptotic pathway is not trigged.
 ...
PMID:[Effects of SODD and survivin on leukemia cell apoptosis induced by chemotherapeutic drugs]. 1760 53

Although meningiomas represent the most common class of tumors of the central nervous system, the molecular events underlying their genesis and development are still not well defined, and therapeutic approaches based on the genetics of these tumors are currently lacking. In the present study we have used the immunoblotting technique to show that the p16(INK4A), Cdk6 and pRB proteins are differentially expressed in primary meningioma cells with 20-, 30- and 36-fold difference between the lowest and the highest levels of each protein, respectively. In addition, we present evidence that the level of the anti-apoptosis survivin protein is high in these benign tumors. Moreover, the annexin V-associated flow cytometry technique was used to show that 60% of meningioma cell cultures underwent apoptosis in response to both gamma-rays and cisplatin, and 50% of these cells exhibited significant sensitivity to hydroxyurea. These agents triggered apoptosis through the mitochondrial pathway, by increasing the Bax/Bcl-2 ratio. Interestingly, the induction of apoptosis following radiation and cisplatin was significant in all cells that expressed low levels of p16(INK4A), Cdk6 and pRB proteins. These data shed more light on the molecular biology of meningioma cells and suggest that survivin and proteins of the RB pathway could play a determinant role in the development and the treatment of meningiomas.
 ...
PMID:Expression of survivin and p16(INK4a)/Cdk6/pRB proteins and induction of apoptosis in response to radiation and cisplatin in meningioma cells. 1804 12

Combined treatment with quercetin and TRAIL induced cytotoxicity and enhanced annexin V staining and poly (ADP-ribose) polymerase (PARP) cleavage in human prostate cancer cell lines DU-145 and PC-3. These indicators of apoptosis resulted from the activation of caspase-8, -9, and -3. Although the expression levels of FLIPs, cIAP1, cIAP2, and the Bcl-2 family were not changed in quercetin-treated cells, significant downregulation of survivin occurred. Knockdown survivin by siRNA significantly increased TRAIL-induced apoptosis. We hypothesized that quercetin-induced activation of MAPK (ERK, p38, JNK) is responsible for downregulation of survivin gene expression. To test this hypothesis, we selectively inhibited MAPK during treatment with quercetin. Our data demonstrated that inhibitor of ERK (PD98059), but not p38 MAPK (SB203580) or JNK (SP600125), significantly maintained the intracellular level of survivin during treatment with quercetin. Interestingly, PD98059 also prevented quercetin-induced deacetylation of histone H3. Data from survivin promoter activity assay suggest that the Sp1 transcription factor binds to the survivin promoter region and quercetin inhibits its binding activity through deacetylation of histone H3. Quercetin-induced activation of the ERK-MSK1 signal transduction pathway may be responsible for deacetylation of histone H3. Taken together, our findings suggest that quercetin enhances TRAIL induced apoptosis by inhibition of survivin expression, through ERK-MSK1-mediated deacetylation of H3.
 ...
PMID:Quercetin augments TRAIL-induced apoptotic death: involvement of the ERK signal transduction pathway. 1837 72

We investigated the difference in survivin expression between a multidrug-resistant lung cancer cell line (H460/cDDP) and its parental counterpart (H460) and the influence of siRNA targeting survivin on the chemosensitivity of H460/cDDP. SiRNA targeting survivin was transfected into H460/cDDP cells using a liposome approach. Survivin mRNA and protein expression were significantly higher in H460/cDDP than H460 cells. The median inhibitory concentrations (IC(50)s) for cisplatin and paclitaxol in vitro against H460/cDDP cells were significantly lower in cells treated with survivin-specific siRNA than in control cells. Apoptosis and cleaved caspase-3 expression were analysed using annexin V and Western blotting, respectively, and showed a significant increase in apoptosis after treatment with the chemotherapeutic agents plus specific siRNA. Specific siRNA sensitized H460/cDDP cells to both cisplatin and paclitaxol. Thus, survivin appears to participate in the multidrug resistance mechanism of H460/cDDP cells and siRNA targeting survivin has the potential to increase the sensitivity of drug-resistant cancer cells to anticancer drugs.
 ...
PMID:Influence of SiRNA targeting survivin on chemosensitivity of H460/cDDP lung cancer cells. 1865 70

Nuclear factor kappaB (NF-kappaB), as an antiapoptotic factor, crucially affects the outcomes of cancer treatments, being one of the major culprits of resistance to chemotherapy. In this study, we investigated whether dehydroxymethylepoxyquinomicin (DHMEQ), a novel NF-kappaB inhibitor, can enhance antitumor activities of taxanes in anaplastic thyroid cancer (ATC) cells. Taxanes induced NF-kappaB activation in ATC cells, which could compromise the therapeutic effect of the drugs. However, DHMEQ, by inhibiting the nuclear translocation of NF-kappaB, completely suppressed the DNA binding capacities of NF-kappaB and lowered the levels of nuclear NF-kappaB protein. Compared with single treatment (either taxane or DHMEQ), the combined treatment strongly potentiated apoptosis, confirmed by cell survival assay; Western blotting for poly (ADP-ribose) polymerase, caspase 3, X-linked inhibitor of apoptosis, and survivin; and flow cytometry for annexin V. Furthermore, we also demonstrate for the first time that the combined treatment showed significantly greater inhibitory effect on tumor growth in a nude mice xenograft model. These findings suggest that taxanes are able to induce NF-kappaB activation in ATC cells, which could attenuate antitumor activities of the drugs, but inhibition of NF-kappaB by DHMEQ creates a chemosensitive environment and greatly enhances apoptosis in taxanes-treated ATC cells in vitro and in vivo. Thus, DHMEQ may emerge as an attractive therapeutic strategy to enhance the response to taxanes in ATCs.
 ...
PMID:Dehydroxymethylepoxyquinomicin, a novel nuclear Factor-kappaB inhibitor, enhances antitumor activity of taxanes in anaplastic thyroid cancer cells. 1865 4

The study was purposed to explore the effect and mechanisms of decitabine and/or Trichostatin A (TSA) on SKM-1 cells in vitro. The effect of decitabine and/or TSA on proliferation of SKM-1cells was analyzed with trypan blue exclusion; the differentiation of SKM-1 cells was detected by nitro-blue tetrazolium (NBT) reduction and flow cytometry; the apoptosis of cells was measured by Annexin V-FITC; the mRNA expression of Fas, survivin and P15(INK4B) in cells treated with decitabine and/or TSA was evaluated by RT-PCR. The results showed that decitabine and/or TSA were capable of inhibiting SKM-1 cell growth and promoting cell differentiation; they stimulated the expression of CD14 and CD11b and inhibited HLA-DR expression; meanwhile and decitabine or/and TSA could induce cell apoptosis, up-regulate mRNA expression of Fas and P15(INK4B), and down-regulate survivin mRNA expression. It is concluded that decitabine can induce apoptosis/differentiation of SKM-1 cells, whose mechanisms may related to the expression of Fas, survivin and P15(INK4B). Decitabine has the synergistic effect with TSA.
 ...
PMID:[Effect of decitabine combined with Trichostatin A on MDS cell line SKM-1 in vitro]. 1871 68

This study is to explore the inhibitory effect of methyl jasmonate on cell proliferation and expression of XIAP and survivin of human neuroblastoma cell line BE(2)-C. After cultivation of 1 - 2 mmol x L(-1) jasmonates with BE (2) -C cells for 6 - 24 h, the growth inhibiting rates of BE (2) -C cells were studied by MTT colorimetry. Cell proliferation was detected by colony formation assay. Cell cycle phases were assayed by propidium iodide staining flow cytometery. Cell apoptosis was inspected by acridine orange-ethidium bromide fluorescent staining, Hoechst 33258 fluorescent staining, and Annexin V-FITC and propidium iodide staining flow cytometry. Expressions of cyclin D1, XIAP and survivin were determined by RT-PCR and real-time RT-PCR. Methyl jasmonate inhibited the growth of BE(2)-C cells in a dose- and time-dependent manner. After addition of 1, 1.5 and 2 mmol x L(-1) of methyl jasmonate for 24 h, the inhibiting rates of cell growth reached 20.6% - 85.5% (P < 0.01), and the IC50 was 1.35 mmol x L(-1). The cell cycles were arrested at S phase. A part of cells presented the characteristic morphological changes of apoptosis. The early apoptotic rates were 13.51%, 17.32%, 24.59% (P < 0.01) and the cell death rates were 29.36% , 54.73% , 75.52% (P < 0.01), respectively. The expression of XIAP and survivin mRNA were downregulated by 18.5% - 68.9% , 22.4% - 48.7% (P < 0.05), respectively, without change in that of cyclin D1. The results indicated that methyl jasmonate could significantly inhibit the growth of BE(2) -C cells through inducing cell cycle arrest and apoptosis, downregulating the expression of XIAP and survivin might be one of its molecular mechanisms of action.
 ...
PMID:[Methyl jasmonate induces apoptosis of human neuroblastoma cell line BE(2) -C and its mechanism]. 1882 59

Survivin, a member of the inhibitor of apoptosis protein family and a target for new drugs, is modulated by reactive oxygen species in several types of neoplasms including leukemias. The aim of this study is to find mechanisms to enhance sensitivity to imatinib in imatinib-responsive cells. In this study, we demonstrated through fluorescein isothiocyanate-labeled annexin V for apoptotic cells detection and western blotting that by inhibiting catalase activity, imatinib apoptosis induction was significantly enhanced (P<0.05) through diminishing survivin expression in K562 cells. These findings might be of clinical relevance and might help improve the chemotherapeutic use of imatinib mesylate.
 ...
PMID:Modulation of reactive oxygen species by antioxidants in chronic myeloid leukemia cells enhances imatinib sensitivity through survivin downregulation. 1882 62

Survivin is an attractive target for tumor growth inhibition and represents a significant approach to anticancer therapy. RNA interference is an important tool for specifically down-regulating the expression of cellular genes. However, the efficiency of short hairpin RNA (shRNA) on the expression of survivin gene and the influence on the cell apoptosis transfected by the non-viral gene transfer system of ultrasound-targeted microbubble destruction was not explored. In this work, recombinant expression plasmid of shRNA targeting survivin gene was constructed and added to cultured cervical cancer cells followed by ultrasound exposure and SonoVue((R)) microbubble. Expression of survivin mRNA and protein were assessed by RT-PCR and western blot analysis. Apoptosis ratio was quantified by flow cytometry marked with annexin V and 7-AAD. After transfected for 48 h, the expression of survivin mRNA and protein were (16.67 +/- 2.73)% and (21.33 +/- 3.55)%, respectively. The apoptosis rate was (45.41 +/- 1.47)%. The differences were significant as compared with other groups (P < 0.01). In conclusion, we suggested that survivin could be regarded as an ideal anticancer target of cervical cancer. Recombinant expression plasmid of shRNA targeting survivin gene mediated by ultrasound-targeted microbubble destruction technique could effectively inhibit the expression of target gene and induce cell apoptosis. This novel method for RNA interference represents a powerful, promising non-viral technology that can be used in the tumor gene therapy and research.
 ...
PMID:Novel ultrasound-targeted microbubble destruction mediated short hairpin RNA plasmid transfection targeting survivin inhibits gene expression and induces apoptosis of HeLa cells. 1899 Oct 17

Osteonecrosis of the jaw secondary to bisphosphonate infusion (zoledronic acid-ZA) is assumed to be a bone disease. This study investigated the effects of ZA on soft tissues using oral mucosal cells as an in vitro model of soft tissue cell death in the pathogenesis of bone necrosis. Human gingival fibroblast and keratinocyte cell lines were exposed to different concentrations of ZA (0.25-3 micromol/l), using 1 micromol/l as the expected baseline concentration. A dose-response effect on apoptosis and cell proliferation [Terminal deoxynucleotidyl transferase-mediated dUTP-Biotin End Labelling and Annexin V or Coulter counter and 3-(4,5-dimethylthiazol-2-yl)-5-(3-carboxymethoxyphenyl)-2-(4-sulfophenyl)-2H-tetrazolium), respectively] was observed with increasing ZA concentrations; both reversed using siRNA against caspase 3 or 9. Gene expression analysis using RT(2) Profiler polymerase chain reaction Arrays demonstrated the differential expression of multiple genes involved in apoptosis including those that encode TNF, BCL-2, Caspase, IAP, TRAF and Death Domain families. Western blot analysis confirmed the presence of activated forms of caspase 3 and 9 and underexpression of survivin protein expression. This study demonstrated that low concentrations of ZA rapidly and directly affected the oral mucosal tissues though the induction of a gene-regulated apoptotic process. These findings support the potential for soft tissue injury as an initiating/potentiating event for osteonecrosis.
 ...
PMID:Effect of zoledronic acid on oral fibroblasts and epithelial cells: a potential mechanism of bisphosphonate-associated osteonecrosis. 1903 17


<< Previous 1 2 3 4 5 6 7 8 9 10 Next >>