1,449 research outputs found
Yc-1, a Novel Potential Anticancer Agent, Inhibit Multidrug-Resistant Protein Via Cgmp-Dependent Pathway
No full textThe aim of the present study was to evaluate the effect of 3 -(5'- hydroxymethyl-2'-furyl)-1-benzylindazole (YC-1) on multidrug resistance. Expression of human P-glycoprotein was assessed by realtime quantitative RT-PCR and western blot. The efflux function of P-glycoprotein was evaluated by rhodamine 123 accumulation and calcein-AM uptake models. The mechanisms of action of YC-1 on different signaling pathways were studied using series of antagonists and the kinetics was also assessed. Cytotoxicity was evaluated by MTT assay. The results demonstrated that increased intracellular accumulation of rhodamine 123 and increased fluorescence of calcein were observed after YC-1 treatment. Furthermore, increased YC-1 concentration resulted in significant decrease in Vmax while K-M remained unchanged suggested that YC-1 acted as a noncompetitive inhibitor of P -glycoprotein. Moreover, the inhibition of Pgp efflux function by YC-1 was significantly reversed by NO synthase inhibitor, (L)- NAME, the sGC inhibitor, ODQ, the PKG inhibitor, Rp-8-Br-PET-cGMPS, and the PKG inhibitor KT5823. In addition, ERK kinase inhibitor PD98059 also significantly restored YC-1 inhibited Pgp efflux function. These results indicated that YC-1 inhibited Pgp efflux via the NO-cGMP-PKG -ERK signaling pathway through noncompetitive inhibition. The present study revealed that YC-1 could be a good candidate for development as a MDR modulator
Synthesis, electrochemistry, absorption and electro-polymerization of aniline-ethynyl metalloporphyrins
No full text[[abstract]]Free-base, nickel(II), zinc(II) and iron(III) mono(4-aniline-ethynyl)biphenylporphines (AEBPPs) were synthesized and their electro-polymerization reactions were studied. Electrochemical and UV-Visible experiments showed that AEBPPs were electro-polymerized onto Pt and indium tin oxide (ITO) surfaces without significantly changing their redox and spectral properties. This suggests that the pi-conjugations of these porphyrins were not greatly affected upon electro-polymerization. SEM images indicated the formation of porphyrin films on the electrode surfaces, while EDS spectra of the metallo-AEBPP films confirmed deposits of the corresponding metals. Upon closer inspection, the AFM images revealed nano-scale ne structure of these porphyrin films. Both SEM and AFM images of the porphyrin films showed similar trends of porphyrin accumulation.[[note]]SC
Association of pancreatic autoantibodies and human leukocyte antigen haplotypes with resolution of diabetes mellitus following therapy for hepatitis C virus infection in patients with human immunodeficiency virus infection
No full textValidity of force platform measures of stance stability under varying sensory conditions. Proceedings of National Science Council, ROC: Part B
No full textA ganglion cyst of posterior cruciate ligment detected by ultrasonographic examination: a case report.
No full textFactors related to meaning of life in Taiwanese women treated with in vitro fertilization.
No full textTheoretical Study on the Correlation between Band Gap, Bandwidth, and Oscillator Strength in Fluorene-Based Donor-Acceptor Conjugated Copolymers
No full textYC-1 inhibits proliferation of breast cancer cells by down-regulating EZH2 expression via activation of c-Cbl and ERK
No full textBACKGROUND AND PURPOSE
YC-1 exhibits potent anticancer activity via numerous actions in many cancer cell lines. Hence, we investigated the in vivo antitumour efficacy of YC-1 in an MDA-MB-468 xenograft model and elucidated the mechanism of down-regulation of enhancer of zeste homology 2 (EZH2) by YC-1 in breast cancer cells.
EXPERIMENTAL APPROACH
In YC-1-treated breast cancer cells and tumour specimens from YC-1-treated MDA-MB-468 xenografts, EZH2 expression was analysed by Western blotting. Pharmacological inhibitors and short hairpin RNA-mediated knockdown were applied to identify possible signalling pathways involved in EZH2 down-regulation by YC-1.
KEY RESULTS
YC-1 reduced the viability of breast cancer cells and tumour growth in MDA-MB-468 xenografts. In breast cancer cells, YC-1 down-regulated EZH2 expression in a concentration-and time-dependent manner. Depletion of EZH2 reduced the proliferation and susceptibility of breast cancer cells to YC-1-induced apoptosis. EZH2 expression was suppressed in tumour specimens from YC-1-treated MDA-MB-468 xenograft mice. YC-1 enhanced both the degradation rate and ubiquitination of EZH2. The down-regulation of EZH2 by YC-1 was associated with activation of PKA and Src-Raf-ERK-mediated signalling pathways. Furthermore, depletion of Casitas B-lineage lymphoma (c-Cbl), an E3 ubiquitin ligase, abolished YC-1-induced apoptosis and suppression of EZH2. YC-1 rapidly activated c-Cbl to induce signalling associated with ERK and EZH2.
CONCLUSION AND IMPLICATIONS
We discovered that YC-1 induces apoptosis and inhibits tumour growth of breast cancer cells via down-regulation of EZH2 by activating c-Cbl and ERK. These data suggest that YC-1 is a potential anticancer drug candidate for triple-negative breast cancer
Involvement of YC-1 in extracellular signal-regulated kinase action in rat cremasteric muscle
No full textAbstractObjectivesThe nitric oxide (NO)–soluble guanylate cyclase (sGC) signalling pathway is attributed to the prevention of ischaemia–reperfusion (I/R)-induced leucocyte–endothelium adhesive interactions. YC-1 (3-(5′-hydroxymethyl-2′-furyl)-1-benzylindazole), a NO-independent sGC activator, has been shown to exert cardiovascular benefits, but its action on leucocyte–endothelium interactions remains unknown. In this study, the direct effect and the underlying mechanism of the anti-adhesive action of YC-1 have been examined in cremasteric microcirculation.MethodsRat cremaster muscle was subjected to 4 h pudic-epigastric artery ischaemia followed by 2 h reperfusion and intravital microscopy was used to observe leucocyte–endothelium interaction and to quantify functional capillaries in rat cremaster muscle flaps.Key findingsThe values for leucocyte rolling, adhering and transmigrating were 5.5-, 6.9- and 8.8-fold greater, respectively, in I/R than in sham-control animals. YC-1 treatment rescued functional capillary density and reduced leucocyte rolling, adhering and transmigrating in I/R injured cremaster muscles to levels observed in sham-controls. Interestingly, these effects were completely blocked by the MEK (extracellular signal-regulated kinase (ERK) kinase) inhibitor (PD98059) but not by sGC or protein kinase C inhibitors. Cotreatment of PD98059 with YC-1 caused a 3.3-, 7.5- and 8.3-fold increase in the values for leucocyte rolling, adhering and transmigrating, respectively, in postcapillary venules of I/R-injured cremaster muscle.ConclusionsThis study has indicated that the anti-adhesive and functional capillary density rescue properties of YC-1 were mediated predominantly by the activation of ERK but not sGC, although YC-1 was identified to be a sGC activator. A better understanding of the action of YC-1 on the microvasculature may help shed light on its therapeutic potential for cardiovascular disease.</jats:sec
YC-1 inhibits proliferation of breast cancer cells by downregulating EZH2 expression via activation of c-Cbl and ERK
No full text[[abstract]]YC-1 exhibits potent anticancer activity via numerous actions in many cancer cell lines. Hence, we investigated the in vivo antitumour efficacy of YC-1 in an MDA-MB-468 xenograft model and elucidated the mechanism of down-regulation of enhancer of zeste homology 2 (EZH2) by YC-1 in breast cancer cells.
EXPERIMENTAL APPROACH:
In YC-1-treated breast cancer cells and tumour specimens from YC-1-treated MDA-MB-468 xenografts, EZH2 expression was analysed by Western blotting. Pharmacological inhibitors and short hairpin RNA-mediated knockdown were applied to identify possible signalling pathways involved in EZH2 down-regulation by YC-1.
KEY RESULTS:
YC-1 reduced the viability of breast cancer cells and tumour growth in MDA-MB-468 xenografts. In breast cancer cells, YC-1 down-regulated EZH2 expression in a concentration- and time-dependent manner. Depletion of EZH2 reduced the proliferation and susceptibility of breast cancer cells to YC-1-induced apoptosis. EZH2 expression was suppressed in tumour specimens from YC-1-treated MDA-MB-468 xenograft mice. YC-1 enhanced both the degradation rate and ubiquitination of EZH2. The down-regulation of EZH2 by YC-1 was associated with activation of PKA and Src-Raf-ERK-mediated signalling pathways. Furthermore, depletion of Casitas B-lineage lymphoma (c-Cbl), an E3 ubiquitin ligase, abolished YC-1-induced apoptosis and suppression of EZH2. YC-1 rapidly activated c-Cbl to induce signalling associated with ERK and EZH2.
CONCLUSION AND IMPLICATIONS:
We discovered that YC-1 induces apoptosis and inhibits tumour growth of breast cancer cells via down-regulation of EZH2 by activating c-Cbl and ERK. These data suggest that YC-1 is a potential anticancer drug candidate for triple-negative breast cancer
- …
