Gene/Protein
Disease
Symptom
Drug
Enzyme
Compound
Pivot Concepts:
Gene/Protein
Disease
Symptom
Drug
Enzyme
Compound
Target Concepts:
Gene/Protein
Disease
Symptom
Drug
Enzyme
Compound
Query: UMLS:C0017636 (
glioblastoma
)
18,345
document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)
Chloride intracellular channel 1
(
CLIC1
) is involved in the development of most aggressive human tumors, including gastric, colon, lung, liver, and
glioblastoma
cancers. It has become an attractive new therapeutic target for several types of cancer. In this work, we aim to identify natural products as potent
CLIC1
inhibitors from Traditional Chinese Medicine (TCM) database using structure-based virtual screening and molecular dynamics (MD) simulation. First, structure-based docking was employed to screen the refined TCM database and the top 500 TCM compounds were obtained and reranked by
X
-Score. Then, 30 potent hits were achieved from the top 500 TCM compounds using cluster and ligand-protein interaction analysis. Finally, MD simulation was employed to validate the stability of interactions between each hit and CLIC1 protein from docking simulation, and Molecular Mechanics/Generalized Born Surface Area (MM-GBSA) analysis was used to refine the virtual hits. Six TCM compounds with top MM-GBSA scores and ideal-binding models were confirmed as the final hits. Our study provides information about the interaction between TCM compounds and CLIC1 protein, which may be helpful for further experimental investigations. In addition, the top 6 natural products structural scaffolds could serve as building blocks in designing drug-like molecules for
CLIC1
inhibition.
...
PMID:Identification of Potent Chloride Intracellular Channel Protein 1 Inhibitors from Traditional Chinese Medicine through Structure-Based Virtual Screening and Molecular Dynamics Analysis. 2914 52
Chloride intracellular channel 1
(
CLIC1
) is highly expressed and secreted by human
glioblastoma
cells and cell lines such as U87, initiating cell migration and tumor growth. Here, we examined whether
CLIC1
could be transferred to human primary microvascular endothelial cells (HMEC). We previously reported that the oncogenic microRNA, miR-5096, increased the release of extracellular vesicles (EVs) by which it increased its own transfer from U87 to surrounding cells. Thus, we also examined its effect on the
CLIC1
transfer. In homotypic cultures, miR-5096 did not increase the expression of
CLIC1
in U87 nor in HMEC. However, the endothelial
CLIC1
level increased after exposure to EVs released by U87, and even more by miR-5096-loaded U87. The EVs-transferred
CLIC1
was active in HMEC, promoting endothelial sprouting in matrigel. Cell exposure to EVs induced cytosolic Ca
2+
spikes which were dependent on the transient receptor potential melastatin member 7 (TRPM7). TRPM7 silencing prevented Ca
2+
spikes and the subsequent
CLIC1
delivery into HMEC. Our data suggest that the vesicular transfer of
CLIC1
between cells requires TRMP7 expression in recipient endothelial cells. How the vesicular transfer of
CLIC1
is modulated in cancer therapy is a future challenge.
...
PMID:The vesicular transfer of CLIC1 from glioblastoma to microvascular endothelial cells requires TRPM7. 3027 61
