Only in Titles

           Search results for: YM-155 Mechanisms: Survivin inhibitor   

paperclip

#28927154   2017/09/20 Save this To Up

Resistance to the mTOR inhibitor everolimus is reversed by the downregulation of survivin in breast cancer cells.

Everolimus (RAD001) is an inhibitor of mammalian target of rapamycin used in combination with exemestane to treat hormone receptor-positive advanced breast cancer. However, not all patients are equally sensitive to RAD001 and certain patients develop resistance. Therefore, the present study analyzed the mechanisms involved in the resistance of breast cancer cells to RAD001 in order to identify a potential tool to overcome it. The effects of RAD001 on the inhibition of cell viability, on the induction of apoptosis and autophagy and on the regulation of survivin, an anti-apoptotic protein, were evaluated in two breast cancer cell lines: BT474 (luminal B) and MCF7 (luminal A). RAD001 was demonstrated to induce autophagy in the two cell lines at following a short period of treatment (4 h) and to induce apoptosis exclusively in BT474 cells following longer periods of treatment (48 h). RAD001 induced the downregulation of survivin in BT474 cells and its upregulation in MCF7 cells. Consequently, inhibiting survivin with YM155 resulted in the acquired resistance of MCF7 cells to RAD001 being reverted, restoring RAD001-induced apoptosis. These data demonstrated that RAD001 exerted anti-proliferative and pro-apoptotic effects on breast cancer cells, but that these effects were repressed by the simultaneous up-regulation of survivin. Finally, the results demonstrated that inhibiting the expression of survivin resulted in the restoration of the anti-neoplastic activity of RAD001.

2552 related Products with: Resistance to the mTOR inhibitor everolimus is reversed by the downregulation of survivin in breast cancer cells.

FDA Standard Frozen Tissu FDA Standard Frozen Tissu FDA Standard Frozen Tissu FDA Standard Frozen Tissu Top 4 types of cancer (co Top 4 types of cancer (co Akt Inhibitor, Isozyme Se mTOR Inhibitor, Ku 006379 mTOR Inhibitor, Ku 006379 AZD-8055 Mechanisms: mTOR BEZ-235 Mechanisms: PI3K INK-128 Mechanisms: mTORC

Related Pathways

paperclip

#28536639   2017/05/24 Save this To Up

Survivin, a molecular target for therapeutic interventions in squamous cell carcinoma.

Squamous cell carcinoma (SCC) is the most common cancer worldwide. The treatment of locally advanced disease generally requires various combinations of radiotherapy, surgery, and systemic therapy. Despite aggressive multimodal treatment, most of the patients relapse. Identification of molecules that sustain cancer cell growth and survival has made molecular targeting a feasible therapeutic strategy. Survivin is a member of the Inhibitor of Apoptosis Protein (IAP) family, which is overexpressed in most of the malignancies including SCC and totally absent in most of the normal tissues. This feature makes survivin an ideal target for cancer therapy. It orchestrates several important mechanisms to support cancer cell survival including inhibition of apoptosis and regulation of cell division. Overexpression of survivin in tumors is also associated with poor prognosis, aggressive tumor behavior, resistance to therapy, and high tumor recurrence. Various strategies have been developed to target survivin expression in cancer cells, and their effects on apoptosis induction and tumor growth attenuation have been demonstrated. In this review, we discuss recent advances in therapeutic potential of survivin in cancer treatment.

1919 related Products with: Survivin, a molecular target for therapeutic interventions in squamous cell carcinoma.

Lung squamous cell carcin Cervix squamous cell carc Esophagus squamous cell c Esophagus squamous cell c Esophageal squamous cell Esophagus squamous cell c Esophageal squamous cell Multiple lung carcinoma ( Skin squamous cell carcin Multiple organ squamous c Esophagus squamous cell c Esophagus squamous cell c

Related Pathways

paperclip

#28435150   2017/04/24 Save this To Up

YM155 Down-Regulates Survivin and Induces P53 Up-Regulated Modulator of Apoptosis (PUMA)-Dependent in Oral Squamous Cell Carcinoma Cells.

BACKGROUND YM155, which inhibits the anti-apoptotic protein survivin, is known to exert anti-tumor effects in various cancers. However, there were few reports describing the inhibitory effect of YM155 on human oral squamous cell carcinoma (OSCC) cells that highly express survivin. In this study, we investigated the anti-tumor effects of YM155 on OSCC cells and then examined its molecular mechanisms. MATERIAL AND METHODS SCC9 cells of OSCC were treated with series of concentrations of YM155 (0.01, 0.1, 1, and 10 ng/ml) for 6, 12, and 24 h. The effect of YM155 on survival of SCC9 cells was detected by MTT and colony formation assay. Cell apoptosis was detected by flow cytometric analysis and the terminal deoxynucleotidyl transferase-mediated dUTP-biotin nick-end labeling (TUNEL) assays. Western blot was used to detect the protein expression of survivin, p53, and PUMA. Caspase-3 activity was measured by cleavage of the caspase-3 substrate. To test the role of PUMA and caspase-3 on YM155-induced apoptosis and growth inhibition, the SCC9 cells was transfected with PUMA siRNA or caspase-3 siRNA or control siRNA for 16 h before YM155 (1 and 10 ng/ml) treatment for 24 h. In addition, we also investigated the effect of YM155 in an in vivo xenograft model. RESULTS Treatment of YM155 efficiently reduced survivin expression and increased PUMA expression and caspase-3 activation in the SCC9 cells. YM155 treatment resulted in 18-86% decrease in cell viability, 10-60% decrease in colony numbers, and 8-40% increase in cell apoptosis (p<0.05 and p<0.01). However, the induction of cell apoptosis growth inhibition was reversed by PUMA siRNA or caspase-3 transfection. In addition, animals treated with YM155 showed more than 60% tumor growth inhibition compared to the controls (p<0.05). CONCLUSIONS YM155 is a potent inhibitor of progression of SCC9 cells, which could be due to attenuation of survivin, and activation of the PUMA/caspase-3 cellular signaling processes. This study suggests that YM155 may be a potential molecular target with therapeutic relevance for the treatment of OSCC.

2797 related Products with: YM155 Down-Regulates Survivin and Induces P53 Up-Regulated Modulator of Apoptosis (PUMA)-Dependent in Oral Squamous Cell Carcinoma Cells.

Oral cavity squamous cell Lung squamous cell carcin Cervix squamous cell carc Esophagus squamous cell c Esophagus squamous cell c Esophageal squamous cell Esophagus squamous cell c Esophageal squamous cell Oral squamous cell cancer Skin squamous cell carcin anti HSV (II) gB IgG1 (mo anti HCMV IE pp65 IgG1 (m

Related Pathways

paperclip

#27459532   2016/07/26 Save this To Up

Proteomics Suggests a Role for APC-Survivin in Response to Somatostatin Analog Treatment of Neuroendocrine Tumors.

Somatostatin analogs are established in the treatment of neuroendocrine tumors (NETs) including small intestinal NET; however, the molecular mechanisms are not well known. Here, we examined the direct effects of lanreotide in NET cell line models.

2999 related Products with: Proteomics Suggests a Role for APC-Survivin in Response to Somatostatin Analog Treatment of Neuroendocrine Tumors.

Anti beta3 AR Human, Poly Recombinant Human Interfe Cell Meter™ Fluorimetri Cell Meter™ Fluorimetri Homogenizer for 24 sample Top five cancer tissue ar Breast invasive ductal ca JUP & APC Protein Protein PTK2 & APC Protein Protei BUB1 & APC Protein Protei APC & CTNNB1 Protein Prot APC & CTNNA1 Protein Prot

Related Pathways

paperclip

#27378269   2016/07/05 Save this To Up

Systematic drug screening reveals specific vulnerabilities and co-resistance patterns in endocrine-resistant breast cancer.

The estrogen receptor (ER) inhibitor tamoxifen reduces breast cancer mortality by 31 % and has served as the standard treatment for ER-positive breast cancers for decades. However, 50 % of advanced ER-positive cancers display de novo resistance to tamoxifen, and acquired resistance evolves in 40 % of patients who initially respond. Mechanisms underlying resistance development remain poorly understood and new therapeutic opportunities are urgently needed. Here, we report the generation and characterization of seven tamoxifen-resistant breast cancer cell lines from four parental strains.

2218 related Products with: Systematic drug screening reveals specific vulnerabilities and co-resistance patterns in endocrine-resistant breast cancer.

Breast cancer tissue arra Breast cancer tissue arra Cancer Apoptosis Phospho- Breast cancer tissue arra Breast cancer (IDC) tissu Breast cancer and adjacen Bladder cancer tissue arr Breast cancer tissue arra Breast cancer tissue arra Breast cancer tissue arra Breast cancer and matched Breast cancer and matched

Related Pathways

paperclip

#27287458   2016/06/20 Save this To Up

Targeting of Survivin Pathways by YM155 Inhibits Cell Death and Invasion in Oral Squamous Cell Carcinoma Cells.

Specific overexpression in cancer cells and evidence of oncogenic functions make Survivin an attractive target in cancer therapy. The small molecule compound YM155 has been described as the first "Survivin suppressant" but molecular mechanisms involved in its biological activity and its clinical potential remain obscure. Survivin protein plays critical roles in oral squamous cell carcinoma (OSCC), suggesting that YM155 would be extremely valuable for OSCC. In this study, we tested our hypothesis whether YM155 could be an effective inhibitor of cell growth, invasion and angiogenesis in oral squamous cell carcinoma (OSCC) cells.

2671 related Products with: Targeting of Survivin Pathways by YM155 Inhibits Cell Death and Invasion in Oral Squamous Cell Carcinoma Cells.

Oral cavity squamous cell Lung squamous cell carcin Cervix squamous cell carc Esophagus squamous cell c Esophagus squamous cell c Esophageal squamous cell Esophagus squamous cell c Esophageal squamous cell Oral squamous cell cancer Skin squamous cell carcin anti HSV (II) gB IgG1 (mo anti HCMV IE pp65 IgG1 (m

Related Pathways

paperclip

#27241169   2016/06/09 Save this To Up

YM155, a small molecule inhibitor of survivin expression, sensitizes cancer cells to hypericin-mediated photodynamic therapy.

Photodynamic therapy (PDT) represents a rapidly developing alternative treatment for various types of cancers. Although considered highly effective, cancer cells can exploit various mechanisms, including the upregulation of apoptosis inhibitors, to overcome the cytotoxic effect of PDT. Survivin, a member of the inhibitor of apoptosis protein family, is known to play a critical role in cancer progression and therapeutic resistance and therefore represents a potential therapeutic target. The aim of this study was to investigate whether YM155, a small molecule inhibitor of survivin expression, can potentiate the cytotoxic effect of hypericin-mediated PDT (HY-PDT). Accordingly, two cell lines resistant to HY-PDT, HT-29 (colorectal adenocarcinoma) and A549 (lung adenocarcinoma), were treated either with HY-PDT alone or in combination with YM155. The efficacy of different treatment regimens was assessed by MTT assay, flow cytometry analysis of metabolic activity, viability, phosphatidylserine externalisation, mitochondrial membrane potential and caspase-3 activity and immunoblotting for the cleavage of poly (ADP-ribose) polymerase (PARP). Here we show for the first time that the repression of survivin expression by YM155 is effective in sensitizing HT-29 and A549 cells to HY-PDT, as measured by the decrease in cell viability and induction of apoptosis. Combined treatment with hypericin and YM155 led to a more severe dissipation of the mitochondrial membrane potential and caused an increase in caspase-3 activation and subsequent PARP cleavage. Our results demonstrate that the repression of survivin expression by YM155 potentially represents a novel alternative strategy to increase the efficacy of HY-PDT in cancer cells that are otherwise weakly responsive or non-responsive to treatment.

2791 related Products with: YM155, a small molecule inhibitor of survivin expression, sensitizes cancer cells to hypericin-mediated photodynamic therapy.

Top five cancer tissue ar Dog Receptor-binding canc GI cancer (esophageal, ga AccuzolTM Total RNA Extra Lung non small cell cance Top 10 cancer tissue arra Oral cavity (tongue and p Oral squamous cell cancer Small intestine disease ( Small intestine disease s Non-small cell lung cance Head & Neck cancer test t

Related Pathways

paperclip

#26957114   2016/04/07 Save this To Up

Targeted inhibition of survivin with YM155 promotes apoptosis of hypoxic human pulmonary arterial smooth muscle cells via the upregulation of voltage-dependent K⁺ channels.

Hypoxic pulmonary hypertension (PH) is a common disease characterized by a disturbance to the balance of apoptosis and cell proliferation in pulmonary artery smooth muscle cells (PASMCs). The anti-apoptotic protein, survivin, has been observed to be upregulated in pulmonary arteries (PAs) of chronic hypoxia-induced PH rats. The present study aimed to investigate the therapeutic potential of sepantronium bromide (YM155), a selective survivin inhibitor, on hypoxic human PASMCs and examine the potential underlying mechanisms. Cultured human PASMCs (HPASMCs) were randomly divided into the following groups: i) Normoxia (N); ii) normoxia + 100 nmol/l YM155 (NY100); iii) hypoxia (H); iv) hypoxia + 1 nmol/l YM155 (HY1); v) hypoxia + 10 nmol/l YM155 (HY10); and hypoxia + 100 nmol/l YM155 (HY100) groups. The cells were exposed to the different conditions for 24 h, according to the group. Cell viability was then determined using a Cell Counting Kit‑8 assay, and apoptosis was detected using a terminal deoxynucleotidyl transferase-mediated deoxyuridine triphosphate nick end labeling assay. The expression levels of survivin were determined using reverse transcription-quantitative polymerase chain reaction (RT-qPCR), immunocytochemistry and Western blot analyses. The expression levels of the voltage-dependent K+ (Kv) channels, Kv1.5 and Kv2.1, were measured using RT-qPCR and Western blotting. Cell proliferation in the hypoxic PASMCs was significantly increased by hypoxia, however, apoptosis of the HPASMCs was suppressed, the expression of survivin were upregulated and the expression levels of Kv1.5 and Kv2.1 were downregulated. YM155 treatment ameliorated the hypoxia‑induced increase in cell proliferation and expression of survivin in a concentration‑dependent manner, increased apoptosis, and increased the expression levels of Kv1.5 and Kv2.1 (P<0.05). By contrast, YM155 treatment in normoxic HPASMCs had no significant effects on proliferation, apoptosis, or the expression levels of survivin and Kv channels in the PASMCs. The present study is the first, to the best of our knowledge, to demonstrate that YM155, a selective survivin inhibitor, has a beneficial therapeutic effect on hypoxic HPASMCs, and that YM155 induces a pro‑apoptotic effect by downregulating the apoptosis inhibitor, survivin, possibly through a Kv channel-mediated mechanism.

2171 related Products with: Targeted inhibition of survivin with YM155 promotes apoptosis of hypoxic human pulmonary arterial smooth muscle cells via the upregulation of voltage-dependent K⁺ channels.

voltage-dependent calcium Alpha Smooth Muscle Actin anti CD7 All T cells Reco anti Transferrin receptor Goat Anti-Human, Mouse, R Ofloxacin CAS Number [824 Actin, Alpha-Smooth Musc Actin, Alpha-Smooth Musc Actin, Alpha-Smooth Musc Anti C Reactive Protein A Epidermal Growth Factor ( Epidermal Growth Factor (

Related Pathways

paperclip

#26557682   2015/11/11 Save this To Up

Curcumin Enhanced Busulfan-Induced Apoptosis through Downregulating the Expression of Survivin in Leukemia Stem-Like KG1a Cells.

Leukemia relapse and nonrecurrence mortality (NRM) due to leukemia stem cells (LSCs) represent major problems following hematopoietic stem cell transplantation (HSCT). To eliminate LSCs, the sensitivity of LSCs to chemotherapeutic agents used in conditioning regimens should be enhanced. Curcumin (CUR) has received considerable attention as a result of its anticancer activity in leukemia and solid tumors. In this study, we investigated the cytotoxic effects and underlying mechanisms in leukemia stem-like KG1a cells exposed to busulfan (BUS) and CUR, either alone or in combination. KG1a cells exhibiting BUS-resistance demonstrated by MTT and annexin V/propidium iodide (PI) assays, compared with HL-60 cells. CUR induced cell growth inhibition and apoptosis in KG1a cells. Apoptosis of KG1a cells was significantly enhanced by treatment with CUR+BUS, compared with either agent alone. CUR synergistically enhanced the cytotoxic effect of BUS. Seven apoptosis-related proteins were modulated in CUR- and CUR+BUS-treated cells analyzed by proteins array analysis. Importantly, the antiapoptosis protein survivin was significantly downregulated, especially in combination group. Suppression of survivin with specific inhibitor YM155 significantly increased the susceptibility of KG1a cells to BUS. These results demonstrated that CUR could increase the sensitivity of leukemia stem-like KG1a cells to BUS by downregulating the expression of survivin.

1691 related Products with: Curcumin Enhanced Busulfan-Induced Apoptosis through Downregulating the Expression of Survivin in Leukemia Stem-Like KG1a Cells.

Macrophage Colony Stimula Macrophage Colony Stimula Anti AGO2 Human, Monoclon Anti AGO2 Mouse, Monoclon Anti AGO2 Human, Monoclon Anti AGO2 Mouse, Monoclon anti HSV (II) gB IgG1 (mo anti HCMV IE pp65 IgG1 (m anti HCMV gB IgG1 (monocl DNA (cytosine 5) methyltr Human Epstein-Barr Virus Jurkat Cell Extract (Indu

Related Pathways

paperclip

#26383166   2015/10/02 Save this To Up

HTLV-1 bZIP Factor RNA and Protein Impart Distinct Functions on T-cell Proliferation and Survival.

Infection of T cells with human T-cell leukemia virus type-1 (HTLV-1) induces clonal proliferation and is closely associated with the onset of adult T-cell leukemia-lymphoma (ATL) and inflammatory diseases. Although Tax expression is frequently suppressed in HTLV-1-infected cells, the accessory gene, HTLV-1 bZIP factor (HBZ), is continuously expressed and has been implicated in HTLV-1 pathogenesis. Here, we report that transduction of mouse T cells with specific mutants of HBZ that distinguish between its RNA and protein activity results in differential effects on T-cell proliferation and survival. HBZ RNA increased cell number by attenuating apoptosis, whereas HBZ protein induced apoptosis. However, both HBZ RNA and protein promoted S-phase entry of T cells. We further identified that the first 50 bp of the HBZ coding sequence are required for RNA-mediated cell survival. Transcriptional profiling of T cells expressing wild-type HBZ, RNA, or protein revealed that HBZ RNA is associated with genes involved in cell cycle, proliferation, and survival, while HBZ protein is more closely related to immunological properties of T cells. Specifically, HBZ RNA enhances the promoter activity of survivin, an inhibitor of apoptosis, to upregulate its expression. Inhibition of survivin using YM155 resulted in impaired proliferation of several ATL cell lines as well as a T-cell line expressing HBZ RNA. The distinct functions of HBZ RNA and protein may have several implications for the development of strategies to control the proliferation and survival mechanisms associated with HTLV-1 infection and ATL.

2402 related Products with: HTLV-1 bZIP Factor RNA and Protein Impart Distinct Functions on T-cell Proliferation and Survival.

Rabbit Anti-Rat Androgen Recombinant Human Androge HTLV 1 gp21 recombinant p Anti C Reactive Protein A Epidermal Growth Factor ( Epidermal Growth Factor ( CELLKINES MACROPHAGE COLO CELLKINES MACROPHAGE COLO CELLKINES PLATELET DERIVE CELLKINES PLATELET DERIVE Rabbit Anti-Human Androge Macrophage Colony Stimula

Related Pathways