scholarly journals Synthesis and Cytotoxic Activity of Chiral Sulfonamides Based on the 2-Azabicycloalkane Skeleton

Molecules ◽  
2020 ◽  
Vol 25 (10) ◽  
pp. 2355 ◽  
Author(s):  
Mahzeiar Samadaei ◽  
Matthias Pinter ◽  
Daniel Senfter ◽  
Sibylle Madlener ◽  
Nataliya Rohr-Udilova ◽  
...  
Keyword(s):  
Hepatocellular Carcinoma ◽  
Cell Viability ◽  
Cytotoxic Activity ◽  
Cell Lines ◽  
Diels Alder ◽  
Human Hepatocellular Carcinoma ◽  
Sulfonyl Chlorides ◽  
Reduce Cell Viability

A series of chiral sulfonamides containing the 2-azabicycloalkane scaffold were prepared from aza-Diels–Alder cycloadducts through their conversion to amines based on 2-azanorbornane or the bridged azepane skeleton, followed by the reaction with sulfonyl chlorides. The cytotoxic activity of the obtained bicyclic derivatives was evaluated using human hepatocellular carcinoma (HCC), medulloblastoma (MB), and glioblastoma (GBM) cell lines. Chosen compounds were shown to notably reduce cell viability as compared to nonmalignant cells.

scholarly journals Upregulation of P2Y2 nucleotide receptor in human hepatocellular carcinoma cells

2016 ◽  
Vol 44 (6) ◽  
pp. 1234-1247 ◽  
Author(s):  
Eunyoung Tak ◽  
Dae Young Jun ◽  
Seok-Hwan Kim ◽  
Gil-Chun Park ◽  
Jooyoung Lee ◽  
...  
Keyword(s):  
Hepatocellular Carcinoma ◽  
Cell Viability ◽  
Cell Lines ◽  
Purinergic Receptor ◽  
Protein A ◽  
Hypoxia Inducible Factor ◽  
Human Hepatocellular Carcinoma ◽  
Hypoxic Conditions ◽  
Hcc Cells

Objective To examine if hypoxia inducible factor-1α (HIF-1α) can induce the upregulation of the purinergic receptor P2Y2 (P2Y2) and thereby promote the viability of human hepatocellular carcinoma (HCC) cells under hypoxic conditions. Methods Archival HCC tumour specimens and corresponding non-cancerous tissues were examined immunohistochemically for P2Y2 protein. A series of in vitro experiments were undertaken using HCC cell lines to determine the effect of hypoxia on HIF-1α and P2Y2 levels, the effect of HIF-1α upregulation on P2Y2 levels, and the effect of P2Y2 upregulation on cell viability under hypoxic conditions. Results Human HCC specimens were positive for P2Y2. Hypoxia and upregulated HIF-1α both upregulated the P2Y2 levels in HCC cell lines. P2Y2 upregulation using plasmid transfection resulted in enhanced cell viability under hypoxia. Treatment of HepG2 cells with the selective P2Y2 antagonist MRS2312 downregulated P2Y2 and reduced cell viability in five HCC cell lines. P2Y2 knockdown reduced HepG2 cell viability under hypoxia. Conclusions These present results suggest that HCC cells upregulate P2Y2 levels during hypoxia, which in turn promotes their growth. P2Y2 could be a potential therapeutic target for treating HCC.

scholarly journals Hepatoblastoma: glutamine depletion hinders cell viability in the embryonal subtype but high GLUL expression is associated with better overall survival

2021 ◽  
Author(s):  
Andreas Schmidt ◽  
Angela Armento ◽  
Ovidio Bussolati ◽  
Martina Chiu ◽  
Verena Ellerkamp ◽  
...  
Keyword(s):  
Hepatocellular Carcinoma ◽  
Overall Survival ◽  
Growth Inhibition ◽  
Cell Viability ◽  
Cell Lines ◽  
Prognostic Significance ◽  
Asparagine Synthetase ◽  
Inhibition Of Proliferation ◽  
Its Gene ◽  
Glutamine Synthesis

Abstract Purpose Glutamine plays an important role in cell viability and growth of various tumors. For the fetal subtype of hepatoblastoma, growth inhibition through glutamine depletion was shown. We studied glutamine depletion in embryonal cell lines of hepatoblastoma carrying different mutations. Since asparagine synthetase was identified as a prognostic factor and potential therapeutic target in adult hepatocellular carcinoma, we investigated the expression of its gene ASNS and of the gene GLUL, encoding for glutamine synthetase, in hepatoblastoma specimens and cell lines and investigated the correlation with overall survival. Methods We correlated GLUL and ASNS expression with overall survival using publicly available microarray and clinical data. We examined GLUL and ASNS expression by RT-qPCR and by Western blot analysis in the embryonal cell lines Huh-6 and HepT1, and in five hepatoblastoma specimens. In the same cell lines, we investigated the effects of glutamine depletion. Hepatoblastoma biopsies were examined for histology and CTNNB1 mutations. Results High GLUL expression was associated with a higher median survival time. Independent of mutations and histology, hepatoblastoma samples showed strong GLUL expression and glutamine synthesis. Glutamine depletion resulted in the inhibition of proliferation and of cell viability in both embryonal hepatoblastoma cell lines. ASNS expression did not correlate with overall survival. Conclusion Growth inhibition resulting from glutamine depletion, as described for the hepatoblastoma fetal subtype, is also detected in established embryonal hepatoblastoma cell lines carrying different mutations. At variance with adult hepatocellular carcinoma, in hepatoblastoma asparagine synthetase has no prognostic significance.

Effect of 5'-fluoro-2'-deoxycytidine and sodium butyrate on the genes of the intrinsic apoptotic pathway, p21, p53, cell viability, and apoptosis in human hepatocellular carcinoma cell lines

2021 ◽  
Author(s):  
Masumeh Sanaei ◽  
Fraidoon Kavoosi ◽  
Mohammad Amin Moezzi
Keyword(s):  
Gene Expression ◽  
Hepatocellular Carcinoma ◽  
Cell Viability ◽  
Cell Lines ◽  
Sodium Butyrate ◽  
Cell Apoptosis ◽  
Chromatin Organization ◽  
Expression Level ◽  
Intrinsic Apoptotic Pathway ◽  
Apoptotic Pathway

Backgrounds: Epigenetic regulation such as DNA methylation plays a major role in chromatin organization and gene transcription. Additionally, histone modification is an epigenetic regulator of chromatin structure and influences chromatin organization and gene expression. The relationship between DNA methyltransferase (DNMTs) expression and promoter methylation of the tumor suppressor genes (TSGs) has been reported in various cancers. Previously, the effect of 5-aza-2'-deoxycytidine (5-AZA-CdR), trichostatin A (TSA), and valproic acid (VPA) was shown on various cancers. This study aimed to investigate the effect of 5'-fluoro-2'-deoxycytidine (FdCyd) and sodium butyrate on the genes of the intrinsic apoptotic pathway, p21, p53, cell viability, and apoptosis in human hepatocellular carcinoma SNU449, SNU475, and SNU368 cell lines. Materials and Methods: In this lab trial study, the SNU449, SNU475, and SNU368 cells were cultured and treated with 5'-fluoro-2'-deoxycytidine and sodium butyrate. To determine cell viability, cell apoptosis, and the relative gene expression level, MTT assay, flow cytometry assay, and qRT-PCR were done respectively. Results: 5'-fluoro-2'-deoxycytidine and sodium butyrate changed the expression level of the BAX, BAK, APAF1, Bcl-2, Bcl-xL, p21, and p53 gene (P<0.0001) by which induced cell apoptosis and inhibit cell growth in all three cell lines, SNU449, SNU475, and SNU368.  Conclusion: Both compounds played their roles through the intrinsic apoptotic pathway to induce cell apoptosis.

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