Browse
Submit Data
Databases
API
Help

Dataset Information

0 Views

0 Connections

0 Citations

0 Reanalyses

0 Downloads

Omics score: 0

Identification of two novel Chlorotoxin derivatives CA4 and CTX-23 with chemotherapeutic and anti-angiogenic potential.

ABSTRACT: Brain tumors are fast proliferating and destructive within the brain microenvironment. Effective chemotherapeutic strategies are currently lacking which combat this deadly disease curatively. The glioma-specific chloride ion channel represents a specific target for therapy. Chlorotoxin (CTX), a peptide derived from scorpion venom, has been shown to be specific and efficacious in blocking glioma Cl(-) channel activity. Here, we report on two new derivatives (termed CA4 and CTX-23) designed and generated on the basis of the peptide sequence alignments of CTX and BmKCT. The novel peptides CA4 and CTX-23 are both effective in reducing glioma cell proliferation. In addition, CTX, CA4 and CTX-23 impact on cell migration and spheroid migration. These effects are accompanied by diminished cell extensions and increased nuclear sizes. Furthermore, we found that CA4 and CTX-23 are selective with low toxicity against primary neurons and astrocytes. In the ex vivo VOGiM, which maintain the entire brain tumor microenvironment, both CTX and CA4 display anti-tumor activity and reduce tumor volume. Hence, CTX and CA4 reveal anti-angiogenic properties with endothelial and angiogenic hotspots disrupting activities. These data report on the identification of two novel CTX derivatives with multiple anti-glioma properties including anti-angiogenesis.

SUBMITTER: Xu T

PROVIDER: S-EPMC4735682 | biostudies-other | 2016 Feb

REPOSITORIES: biostudies-other

ACCESS DATA

Json Xml

Similar Datasets

Human RNASET2 derivatives as potential anti-angiogenic agents: actin binding sequence identification and characterization.

Project description:Human RNASET2 (hRNASET2) has been demonstrated to exert antiangiogenic and antitumorigenic effects independent of its ribonuclease capacity. We suggested that RNASET2 exerts its antiangiogenic and antitumorigenic activities via binding to actin and consequently inhibits cell motility. We focused herein on the identification of the actin binding site of hRNASET2 using defined sequences encountered within the whole hRNASET2 protein. For that purpose we designed 29 different hRNASET2-derived peptides. The 29 peptides were examined for their ability to bind immobilized actin. Two selected peptides-A103-Q159 consisting of 57 amino acids and peptide K108-K133 consisting of 26 amino acids were demonstrated to have the highest actin binding ability and concomitantly the most potent anti-angiogenic activity. Further analyses on the putative mechanisms associated with angiogenesis inhibition exerted by peptide K108-K133 involved its location during treatment within the HUVE cells. Peptide K108-K133 readily penetrates the cell membrane within 10 min of incubation. In addition, supplementation with angiogenin delays the entrance of peptide K108-K133 to the cell suggesting competition on the same cell internalization route. The peptide was demonstrated to co-localize with angiogenin, suggesting that both molecules bind analogous cellular epitopes, similar to our previously reported data for ACTIBIND and trT2-50.

| S-EPMC4341462 | biostudies-literature

Novel Adamantane-Linked Isothiourea Derivatives as Potential Chemotherapeutic Agents: Synthesis, Structural Insights, and Antimicrobial/Anti-Proliferative Profiles

Project description:In this study, two

| S-EPMC10099428 | biostudies-literature

Identification and Functional Characterization of Anti-metastasis and Anti-angiogenic Activities of Triethylene Glycol Derivatives.

Project description:We had previously reported anticancer activity in the water extract (WEX) of Ashwagandha leaves, and identified Triethylene glycol (TEG) as an active tumor suppressor component. In this study, we investigated anti-migratory and anti-angiogenesis activities of WEX and TEG. We conducted in vitro and in vivo experiments using TEG, and its two derivatives, Triethyleneglycol dimethacrylate (TD-10), and Tetraethyleneglycol dimethacrylate (TD-11). The data revealed strong anticancer and anti-metastasis potentials in the derivatives. Non-toxic, anti-migratory doses of the derivatives showed inhibition of canonical Wnt/β-catenin axis and consequent downregulation of EMT-signaling proteins (Vimentin, MMPs and VEGF). These results endorse that the TD-10 and TD-11 have potential to safely put a check on the aggressiveness of the metastatic cells and therefore represent promising candidates for the treatment of metastatic cancers.

| S-EPMC6279921 | biostudies-literature

7-epi-Clusianone, a Multi-Targeting Natural Product with Potential Chemotherapeutic, Immune-Modulating, and Anti-Angiogenic Properties.

Project description:Targeted therapies have changed the treatment of cancer, giving new hope to many patients in recent years. The shortcomings of targeted therapies including acquired resistance, limited susceptible patients, high cost, and high toxicities, have led to the necessity of combining these therapies with other targeted or chemotherapeutic treatments. Natural products are uniquely capable of synergizing with targeted and non-targeted anticancer regimens due to their ability to affect multiple cellular pathways simultaneously. Compounds which provide an additive effect to the often combined immune therapies and cytotoxic chemotherapies, are exceedingly rare. These compounds would however provide a strengthening bridge between the two treatment modalities, increasing their effectiveness and improving patient prognoses. In this study, 7-epi-clusianone was investigated for its anticancer properties. While previous studies have suggested clusianone and its conformational isomers, including 7-epi-clusianone, are chemotherapeutic, few cancer types have been demonstrated to exhibit sensitivity to these compounds and little is known about the mechanism. In this study, 7-epi-clusianone was shown to inhibit the growth of 60 cancer cell types and induce significant cell death in 25 cancer cell lines, while simultaneously modulating the immune system, inhibiting angiogenesis, and inhibiting cancer cell invasion, making it a promising lead compound for cancer drug discovery.

| S-EPMC6930650 | biostudies-literature

Identification of Novel Transcriptome Signature as a Potential Prognostic Biomarker for Anti-Angiogenic Therapy in Glioblastoma Multiforme.

Project description:Glioblastoma multiforme (GBM) is the most common and devastating type of primary brain tumor, with a median survival time of only 15 months. Having a clinically applicable genetic biomarker would lead to a paradigm shift in precise diagnosis, personalized therapeutic decisions, and prognostic prediction for GBM. Radiogenomic profiling connecting radiological imaging features with molecular alterations will offer a noninvasive method for genomic studies of GBM. To this end, we analyzed over 3800 glioma and GBM cases across four independent datasets. The Chinese Glioma Genome Atlas (CGGA) and The Cancer Genome Atlas (TCGA) databases were employed for RNA-Seq analysis, whereas the Ivy Glioblastoma Atlas Project (Ivy-GAP) and The Cancer Imaging Archive (TCIA) provided clinicopathological data. The Clinical Proteomic Tumor Analysis Consortium Glioblastoma Multiforme (CPTAC-GBM) was used for proteomic analysis. We identified a simple three-gene transcriptome signature-SOCS3, VEGFA, and TEK-that can connect GBM's overall prognosis with genes' expression and simultaneously correlate radiographical features of perfusion imaging with SOCS3 expression levels. More importantly, the rampant development of neovascularization in GBM offers a promising target for therapeutic intervention. However, treatment with bevacizumab failed to improve overall survival. We identified SOCS3 expression levels as a potential selection marker for patients who may benefit from early initiation of angiogenesis inhibitors.

| S-EPMC7957709 | biostudies-literature

Identification of Novel Transcriptome Signature as a Potential Prognostic Biomarker for Anti-Angiogenic Therapy in Glioblastoma Multiforme.

| S-EPMC7564118 | biostudies-literature

Synthesis and cytotoxic studies of novel 5-phenylisatin derivatives and their anti-migration and anti-angiogenic evaluation.

Project description:A number of 5-arylisatin derivatives were synthesized in 5-6 steps from readily available starting materials. Their structures were confirmed by 1H NMR and 13C NMR as well as LC/MS. The cytotoxicity of these novel isatins against human leukemia K562?cells were evaluated by MTT assay in vitro. SAR studies indicated that the N-substituted benzyl and C-5 substituted phenyl groups greatly enhance their cytotoxic activity, whereas an intact carbonyl functionality on C-3 present in the parent ring is required to maintain such a potency. Particularly, N-(p-methoxybenzyl)-5-(p-methoxyphenyl)isatin (compound 2m) showed the highest antitumor activity against K562?cell lines (IC50?=?0.03??M). Moreover, treatment with compound 2m significantly inhibited liver cancer HepG2 cells proliferation and migration, which could also reduce the human umbilical vein endothelial cells (HUVEC) tube formation. In conclusion, compound 2m exhibited very good cancer cells proliferation inhibition by angiogenesis responses in vitro, and 2m might be a promising angiogenesis inhibitor for cancer treatment.

| S-EPMC7115506 | biostudies-literature

Anti-angiogenic activity of rPAI-1(23) and vasa vasorum regression.

Project description:The vasa vasorum are unique networks of vessels that become angiogenic in response to changes in the vessel wall. Structural studies, using various imaging modalities, show that the vasa vasorum form a plexus of microvessels during the atherosclerotic disease process. The events that stimulate vasa vasorum neovascularization remain unclear. Anti-angiogenic molecules have been shown to inhibit/regress the neovascularization; they provide significant insight into vasa vasorum function, structure, and specific requirements for growth and stability. This review discusses evidence for and against potential stimulators of vasa vasorum neovascularization. Anti-angiogenic rPAI-123, a truncated isoform of plasminogen activator inhibitor-1 (PAI-1) stimulates a novel pathway for regulating plasmin activity. This mechanism contributes significantly to vasa vasorum regression/collapse and is discussed as a model of regression.

| S-EPMC3624061 | biostudies-literature

The novel CTX-M-116 β-lactamase gene discovered in Proteus mirabilis is composed of parts of the CTX-M-22 and CTX-M-23 genes.

Project description:The novel β-lactamase gene bla(CTX-M-116) was identified in a Proteus mirabilis nosocomial isolate recovered from the urine of a patient in Moscow in 2005. DNA sequence analysis showed bla(CTX-M-116) to be a hybrid gene consisting of 5' bla(CTX-M-23) (nucleotides 1 to 278) and 3' bla(CTX-M-22) (nucleotides 286 to 876) moieties separated by an intervening putative site of recombination (GTTAAAT). A retrospective analysis of available bla(CTX-M) genes in the GenBank database revealed 19 bla(CTX-M) genes that display the same hybrid structure.

| S-EPMC3591887 | biostudies-literature

Azaindole derivatives are inhibitors of microtubule dynamics, with anti-cancer and anti-angiogenic activities.

Project description:Background and purposeDrugs targeting microtubules are commonly used for cancer treatment. However, the potency of microtubule inhibitors used clinically is limited by the emergence of resistance. We thus designed a strategy to find new cell-permeable microtubule-targeting agents.Experimental approachUsing a cell-based assay designed to probe for microtubule polymerization status, we screened a chemical library and identified two azaindole derivatives, CM01 and CM02, as cell-permeable microtubule-depolymerizing agents. The mechanism of the anti-tumour effects of these two compounds was further investigated both in vivo and in vitro.Key resultsCM01 and CM02 induced G2/M cell cycle arrest and exerted potent cytostatic effects on several cancer cell lines including multidrug-resistant (MDR) cell lines. In vitro experiments revealed that the azaindole derivatives inhibited tubulin polymerization and competed with colchicines for this effect, strongly indicating that tubulin is the cellular target of these azaindole derivatives. In vivo experiments, using a chicken chorioallantoic xenograft tumour assay, established that these compounds exert a potent anti-tumour effect. Furthermore, an assay probing the growth of vessels out of endothelial cell spheroids showed that CM01 and CM02 exert anti-angiogenic activities.Conclusions and implicationsCM01 and CM02 are reversible microtubule-depolymerizing agents that exert potent cytostatic effects on human cancer cells of diverse origins, including MDR cells. They were also shown to inhibit angiogenesis and tumour growth in chorioallantoic breast cancer xenografts. Hence, these azaindole derivatives are attractive candidates for further preclinical investigations.

| S-EPMC3579287 | biostudies-literature

OmicsDI is part of the ELIXIR infrastructure

OmicsDI is an Elixir interoperability service. Learn more ›

Tweets

OmicsDI Databases

PRIDE
PeptideAtlas
MassIVE
JPOST Repository
Physiome Model Repository

EGA
EVA
ENA
LINCS
PAXDB
Cell Collective

MetaboLights
Metabolomics Workbench
MetabolomeExpress
GNPS
BioModels
FAIRDOMHub

ArrayExpress
dbGaP
ExpressionAtlas
GEO
NODE

Information

Databases
Help
API
Contact us
Code on GitHub
Terms of use
Submit Data