RYBP activates PARP-1 induced Parthanatos in esophageal squamous cell carcinoma cells and enhances response to YM155 / 西安交通大学学报(医学版)

【Objective】 To explore the role of RYBP in activating PARP-1 dependent Parthanatos and promoting response to YM155 in esophageal squamous cell carcinoma. 【Methods】 CCK-8 and flow cytometry were used to analyze the inhibition ratio and cell death percentage after YM155 treatment in both RYBP overexpression group and control group. Western blotting was used to detect the expression of Parthanatos-related proteins. 【Results】 Compared with control group, RYBP overexpression group showed higher inhibition ratio and cell death percentage after YM155 treatment. Overexpression of RYBP activated PARP-1 with or without YM155 treatment. Besides, after YM155 treatment, KYSE170-RYBP showed more PAR accumulation in the nucleus, AIF translocation from mitochondria to the nucleus than control cells. 【Conclusion】 RYBP can activate PARP-1/PAR/AIF-dependent induced Parthanatos in esophageal squamous cell carcinoma and enhance response to YM155.

High-throughput screening identifies established drugs as SARS-CoV-2 PLpro inhibitors

A new coronavirus (SARS-CoV-2) has been identified as the etiologic agent for the COVID-19 outbreak. Currently, effective treatment options remain very limited for this disease; therefore, there is an urgent need to identify new anti-COVID-19 agents. In this study, we screened over 6,000 compounds that included approved drugs, drug candidates in clinical trials, and pharmacologically active compounds to identify leads that target the SARS-CoV-2 papain-like protease (PLpro). Together with main protease (M

Survivin inhibitor YM155 induces apoptosis of thyroid carcinoma cell line B-CPAP and potential mechanisms / 中国免疫学杂志

Objective:To investigate the effects of survivin inhibitor YM155{1-(2-methoxyethyl)-2-methyl-4,9-dioxo-3-(pyrazin-2-ylmethyl)-4,9-dihydro-1H-naphtho[2,3-d] imidazolium bromide} on cell viability,apoptosis and Cysteinyl aspartate specific proteinase-3,Cysteinyl aspartate specific proteinase-8,Cysteinyl aspartate specific proteinase-9 of the thyroid carcinoma cell line B-CPAP in order to discuss mitochondrial mechanisms of apoptosis.Methods: B-CPAP cells were cultured in vitro and treated with YM155 at various concentrations(0,0.5,1,2,4,8 nmol/L)for 24,48 and 72h.The cell viability of B-CPAP cells were measured by CCK-8 assay.B-CPAP cells were randomly divided into 4 groups:B-CPAP cells were treated with YM155 at various concentrations(0,1,2 nmol/L)and 5 μmol/L Cisplatin(the positive control group)for 24 h.The effects of YM155 on B-CPAP cells apoptosis were evaluated by TUNEL and flow cytometry Annexin V-FITC/PI method.The expression level of Survivin and Caspase-3,Caspase-8 ,Caspase-9 were detected by Western blot analysis.Results: Compared with the 0 nmol/L group,YM155 significantly inhibited the cell viability of B-CPAP cells and induced their apoptosis (P<0.05 or P<0.01).Compared with the 0 nmol/L group,YM155 significantly reduced the expression level of Survivin and upregulated Caspase-3,Caspase-8 ,Caspase-9(P<0.05 or P<0.01).Conclusion: YM155 can inhibit the cell viability of B-CPAP cells and induce apoptosis,its possible mechanisms maybe related to upregulated expression level of Caspase-3,Caspase-8 and Caspase-9.

Effects of survivin inhibitor YM155 on mitochondrial apoptotic pathway of retinoblastoma Y79 cells / 中国病理生理杂志

AIM:To investigate the effects of survivin inhibitor YM155 {4,9-dihydro-1-(2-methoxyethyl)-2-methyl-4,9-dioxo-3-(2-pyrazinylmethyl)-4,9-dihydro-1H-naphtho[2,3-d]imidazolium bromide} on the apoptosis, mito-chondrial membrane potential (Δψm) and cytochrome C (Cyt C) of retinoblastoma Y79 cells, and to analyze the mitochon-drial mechanisms of apoptosis .METHODS:Y79 cells were cultured in vitro and treated with YM155 at concentrations of 0, 0.5, 1, 2, 4 and 8 nmol/L.The cells in control group were treated without YM 155.The proliferation of Y79 cells were measured by CCK-8 assay and bromodeoxyuridine ( BrdU) labeling assay .Y79 cells were randomly divided into 4 groups:control group ( with equal volume of RPMI-1640 nutrient medium ) , positive control group ( 10 nmol/L topotecan ) , low-dose (1 nmol/L) YM155 group and high-dose (2 nmol/L) YM155 group.The effects of YM155 on the apoptosis, the changes of Δψm , the mitochondrial distribution and the protein level of Cyt C in the Y 79 cells were evaluated by flow cytom-etry with Annexin V-FITC/PI staining, JC-1 staining, immunofluorescence analysis and Western blot , respectively.RE-SULTS:Compared with control group , YM155 significantly inhibited the proliferation of Y 79 cells and induced apoptosis (P<0.05).YM155 significantly reduced Δψm of the Y79 cells, promoted Cyt C which released from mitochondria to the cytosol and reduced the protein level of Cyt C in the mitochondria (P<0.05).CONCLUSION:YM155 inhibits Y79 cell proliferation and induces apoptosis , and the possible mechanisms may be involved in the mitochondrium-mediated apoptotic pathway .

Effects of YM155 on proliferation and apoptosis of triple negative breast cancer MDA-MB-231 cells / 中华内分泌外科杂志

Objective To investigate the apoptosis induction effects and the possible mechanism of YM155 on triple negative breast cancer MDA-MB-231cells.Methods MDA-MB-231 cells were treated with dif-ferent concentrations of YM 155, and the survival rate of the cells was determined by CCK-8 assay and the half maximal inhibitory concentration ( IC50 ) value of YM155 was calculated .The apoptosis rate was examined by An-nexin V-FITC/PI double staining.mRNA expression of survivin and bcl-2 in MDA-MB-231cells was detected by RT-PCR.The protein expression of survivin , bcl-2, caspase-3, and PARP were detected by Western blot .Re-sults YM155 significantly inhibited the growth of MDA-MB-231 cells in a dose-and-time-dependenct way .IC50 was(1.749 ±0.265) ng/ml and(0.823 ±0.125) ng/ml respectively at 24 and 48 hours.The apoptosis rate of cells treated with 0.5 ng/ml, 1.0 ng/ml, and 1.5 ng/ml YM155 was (10.93 ±0.94)%,(31.10 ±1.51)%, and(46.83 ±2.92)%respectively, which had significant difference compared to that of the control group (6.4 ± 1.2)%(P<0.01).YM155 could significantly decrease mRNA and protein expression of surviving , besides, it reduced bcl-2 expression and increased caspase-3 and PARP protein expression .Conclusions YM155 can ef-fectively induce the apoptosis of MDA-MB-231 cells by downregulating survivin and activating caspase pathway . Bcl-2 might play a role in the apoptosis .