Implication of Egr-1 in trifluoperazine-induced growth inhibition in human U87MG glioma cells

Abstract

A bstractThe early grow th response gene-1 (Egr-1) is a tum or suppressor which plays an im portant role in cell growth, differentiation and apoptosis. Egr-1 has been shown to be down-regulated in m any types of tum or tissues. Trifluoperazine (TFP), a phenothiazine class of antipsychotics, restored serum -induced Egr-1 expression in several cancer cell lines. W e investigated the effect of Egr-1 expression on the TFP-induced inhibition of cell growth. Ectopic expression of Egr-1 enhanced the TFP-induced antiproliferative activity and downregulated cyclin D1 level in U87M G gliom a cells. Our results suggest that antipsychotics TFP exhibits antiproliferative activity through up-regulation of Egr-1.

Molecular mechanism of trifluoperazine induces apoptosis in human A549 lung adenocarcinoma cell lines

“…In addition to its irreversible effect on cell growth, an observed decrease in cell number was also apparently caused by cell apoptosis. Our findings support the results of previous studies (20)(21)(22)(23), indicating that TFP induced marked apoptosis in A549 cells. The induction of apoptotic death was accompanied by characteristic morphological changes, such as nuclear condensation and the formation of apoptotic bodies (Fig.…”

“…Calmodulin is a ca 2+ -binding protein that is ubiquitously expressed in almost all eukaryotic cells and plays a key role in mediating diverse Ca 2+ -dependent physiological responses, including the regulation of cell proliferation. It has been reported that, as a calmodulin antagonist, TFP inhibited cell proliferation and invasion and induced apoptosis in several types of cancer cells (20)(21)(22)(23).…”

Chlorpromazine activates p21Waf1/Cip1gene transcription via early growth response-1 (Egr-1) in C6 glioma cells

“…In contrast, Egr-1 plays an essential role in prostate tumor epithelial cells Virolle et al, 2003). Previously, we reported that Trifluoperazine (TFP), a phenothiazine derivative, upregulates Egr-1 expression in cells (Shin et al, 2004), suggesting that Egr-1 expresses growth suppressor activity, at least in gliomas. Introduction of functional Egr-1 into human glioma primary cells results in growth arrest and eventual cell death (Calogero et al, 2004).…”

Identification and functional characterization of an alternative splice variant within the fourth exon of human nanog

“…Protein samples (20 µg) were separated by 10% SDS-polyacrylamide gel electrophoresis and transferred to nitrocellulose filters. Blots were incubated with primary antibodies and developed using an enhanced chemiluminescence detection system (Amersham Pharmacia Biotech., Piscataway, NJ) as previously described (Shin et al, 2004).…”