Gene/Protein Disease Symptom Drug Enzyme Compound
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Query: UNIPROT:P10415 (Bcl-2)
 33,771 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

We used a standardized electrophoresis protocol to identify differentially expressed proteins based on a sample pooling approach comparing three follicular lymphoma and three mantle cell lymphoma-derived cell lines. One hundred and seventy-five consistently differentially expressed proteins were identified out of more than 1600 protein spots per gel. Of these 175 protein spots, 38 of the 41 most highly expressed proteins were identified by MS analysis (MALDI-TOF), involving different cellular programs such as DNA repair (Rad50), cell cycle control (Mad1L1), transcription (SAFB), and apoptosis (Luca-15 protein). Expression data were confirmed by Western blot analysis of identified proteins and 2-D gel hybridization of proteins with known overexpression (G1/S-specific cyclin-D1, apoptosis regulator Bcl-2). Comparison of proteome analysis to RNA expression array data revealed only a modest correlation of RNA and protein level emphasizing the relevance of post-translational regulation in lymphomagenesis (p = 0.36). Most interestingly, additional data bank search identified 13 out of 17 referenced proteins (76%) as members of a TP53-dependent network of cell regulation.
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PMID:Proteome- and microarray-based expression analysis of lymphoma cell lines identifies a p53-centered cluster of differentially expressed proteins in mantle cell and follicular lymphoma. 1799 Feb 59

We have previously provided evidence showing an association between some precursor lesions with low nuclear grade breast carcinomas (LNGBCs). In this study, further immunophenotypic support to our proposed route of pathogenesis of LNGBC and their precursor lesions was provided. Precursor lesions including columnar cell lesions, atypical ductal hyperplasia, ductal carcinoma in situ, usual epithelial hyperplasia, and lobular neoplasia were compared with matching "morphologically normal" terminal lobular duct units and matching invasive carcinoma. The epithelial cells in the putative precursor flat epithelial atypia, atypical ductal hyperplasia, lobular neoplasia, ductal carcinoma in situ lesions, and their coexisting LNGBC were negative for basal and myoepithelial markers, but positive for CK19/18/8, estrogen receptor (ER)-alpha, Bcl-2, and cyclin D1. The ER-alpha/ER-beta expression ratio increased during carcinogenesis, as did expression of cyclin D1 and Bcl-2. p53 immunopositivity was found 3% in LNGBC versus 43% in high nuclear grade breast carcinoma (HNGBC), whereas ataxia telangiectasia mutated expression was absent or reduced in 22% of LNGBC versus 53% of HNGBC cases. In summary, our findings support the concept that flat epithelial atypia is the earliest morphologically identifiable nonobligate precursor lesion of LNGBC. These may represent a family of precursor, in situ and invasive neoplastic lesions belonging to the luminal "A" subclass of breast cancer. The balance between ER-alpha and ER-beta expression may be important in driving cyclin D-1 and Bcl-2 expression. Ataxia telangiectasia mutated may be one of the alternative regulatory mechanisms to TP53 mutation or dysfunction in low-grade and high-grade breast carcinoma. Our findings support the concept that progression of LNGBC to HNGBC (basal-like or HER2+) phenotype is an unlikely biologic phenomenon.
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PMID:Morphologic and molecular evolutionary pathways of low nuclear grade invasive breast cancers and their putative precursor lesions: further evidence to support the concept of low nuclear grade breast neoplasia family. 1822 78

Berberine is an isoquinoline plant alkaloid with a long history of being used for the treatment of many diseases in Chinese herbal medicine. Berberine has a wide range of biochemical and pharmacological effects, including antitumor activities, but its mechanism of action is not clearly understood. In this study, we investigated that the relationship between the antiproliferative activities of berberine and the apoptotic pathway associated with its molecular mechanism of action in human glioblastoma T98G cells. Berberine treatment of T98G cell lines inhibited cell proliferation and induced cell death in a dose (50-200 microg/ml) dependent manner with an IC50 value of 134 microg/ml, which was associated with an increase in G1 arrest. Western blot analysis showed that the berberine-induced G1 arrest was mediated through the increased expression of P27 and the decreased expression of cyclin-dependent kinase (CDK) 2, CDK4, cyclin D, and cyclin E proteins. Berberine treatment also markedly enhanced apoptosis in T98G cells through the induction of a higher ratio of the Bax/Bcl-2 proteins, the disruption of mitochondrial membrane potential, and the activation of procaspase-9, caspase-9, caspase-3, and poly(ADP-ribose) polymerase (PARP). Berberine can inhibit T98G cell proliferation by inducing G1 arrest and apoptosis. These results demonstrate that the berberine-induced apoptosis of T98G cells is primarily mediated through the mitochondrial/caspases-dependent pathway.
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PMID:Berberine induces G1 arrest and apoptosis in human glioblastoma T98G cells through mitochondrial/caspases pathway. 1837 40

We examined the effect of (-)-syringaresinol, a furofuran-type lignan isolated from Daphne genkwa, on cell cycle regulation in HL-60 human promyelocytic leukemia cells in vitro. (-)-Syringaresinol decreased the viability of HL-60 cells by inducing G(1) arrest followed by apoptosis in a dose- and time-dependent manner. The G(0)/G(1) phase of the cell cycle is regulated by cyclin-dependent kinases (Cdk), cyclins and cyclin-dependent kinase inhibitors (Cdki). We show by western blot analysis, that the (-)-syringaresinol-induced G(1) arrest was mediated through the increased expression of Cdki proteins (p21(cip1/waf1) and p27(kip1)) with a simultaneous decrease in cdk2, cdk4, cdk6, cyclin D(1), cyclin D(2), and cyclin E expression. The induction of apoptosis after treatment with (-)-syringaresinol for 24 h was demonstrated by morphological changes, DNA fragmentation, altered ratio of Bax/Bcl-2, cleavage of poly(ADP-ribose) polymerase and flow cytometry analysis. (-)-Syringaresinol also induced cytochrome c release and activation of caspase-3 and caspase-9. To our knowledge, this is the first time that (-)-syringaresinol has been reported to potently inhibit the proliferation of human promyelocytic HL-60 cells through G(1) arrest and induction of apoptosis. These findings suggest that (-)-syringaresinol may be a potential chemotherapeutic agent for the treatment of cancer.
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PMID:(-)-Syringaresinol inhibits proliferation of human promyelocytic HL-60 leukemia cells via G1 arrest and apoptosis. 1848 7

This study investigates the anticancer effect of dehydrocostuslactone (DHE), a plant-derived sesquiterpene lactone, on human breast cancer cells. DHE inhibits cell proliferation by inducing cells to undergo cell cycle arrest and apoptosis. DHE suppresses the expression of cyclin D, cyclin A, cyclin-dependent kinase 2, and cdc25A and increases the amount of p53 and p21, resulting in G(0)/G(1)-S phase arrest in MCF-7 cells. In contrast, DHE caused S-G(2)/M arrest by increasing p21 expression and chk1 activation and inhibiting cyclin A, cyclin B, cdc25A, and cdc25C expression in MDA-MB-231 cells. DHE induces up-regulation of Bax and Bad, down-regulation of Bcl-2 and Bcl-XL, and nuclear relocation of the mitochondrial factors apoptosis-inducing factor and endonuclease G. We also found that DHE inhibits survival signaling through the Janus tyrosine kinase-signal transducer and activator of transcription-3 signaling by increasing the expression of suppressors of cytokine signaling (SOCS)-1 and SOCS-3. Reduction of SOCS-1 and SOCS-3 expression by small interfering RNA inhibits DHE-mediated signal transducer and activator of transcription-3 inhibition, p21 up-regulation, and cyclin-dependent kinase 2 blockade, supporting the hypothesis that DHE inhibits cell cycle progression and cell death through SOCS-1 and SOCS-3. Significantly, animal studies have revealed a 50% reduction in tumor volume after a 45-day treatment period. Taken together, this study provides new insights into the molecular mechanism of the DHE action that may contribute to the chemoprevention of breast cancer.
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PMID:Dehydrocostuslactone disrupts signal transducers and activators of transcription 3 through up-regulation of suppressor of cytokine signaling in breast cancer cells. 1938 49

Porphyromonas gingivalis is an oral pathogen that is also associated with serious systemic conditions such as preterm delivery. Here we investigated the interaction between P. gingivalis and a cell line of extravillous trophoblasts (HTR-8) derived from the human placenta. P. gingivalis internalized within HTR-8 cells and inhibited proliferation through induction of arrest in the G1 phase of the cell cycle. G1 arrest was associated with decreased expression of cyclin D and of CDKs 2, 4 and 6. In addition, levels of CDK inhibitors p15, p16, p18 and p21 were increased following P. gingivalis infection. The amount of Rb was diminished by P. gingivalis, and transient overexpression of Rb, with concomitant upregulation of phospho-Rb, relieved P. gingivalis-induced G1 arrest. HTR-8 cells halted in the G1 phase became apoptotic, and apoptosis was accompanied by an increase in the ratio of Bax/Bcl-2 and increased activity of caspases 3, 7 and 9. HTR-8 cells infected with P. gingivalis also exhibited a sustained activation of ERK1/2, and knock-down of ERK1/2 activity with siRNA abrogated both G1 arrest and apoptosis. Thus, P. gingivalis can invade placental trophoblasts and induce G1 arrest and apoptosis through pathways involving ERK1/2 and its downstream effectors, properties that provide a mechanistic basis for pathogenicity in complications of pregnancy.
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PMID:Porphyromonas gingivalis invades human trophoblasts and inhibits proliferation by inducing G1 arrest and apoptosis. 1952 55

Most cells in the body are in a resting state and undergo cell cycle progression only upon growth factor stimulation or activation. while much research on proliferation and activation has been performed, very little about signals that maintain quiescent cells in G(0) is known, preventing cell cycle entry or apoptosis. In this study, the pathways of apoptosis induction in quiescent peripheral blood cells and fibroblasts mediated by inhibition or downregulation of Dipeptidyl Peptidase 2 (DPP2) have been explored. A decrease in DPP2 activity was found to cause resting cells to exit from G(0), accompanied by a decrease in p130, p27(Kip1) and p21(Cip1) protein levels. In addition, DPP2-inhibited or downregulated cells exhibit an increase in early G(1)/S progressors, with increases in the levels of retinoblastoma (pRb), p107 and cyclin D proteins. Furthermore, decrease of DPP2 activity leads to an increase in c-Myc and a decrease in Bcl-2, two events that have been associated with apoptosis induction. This apoptosis by DPP2 downregulation is prevented in p53(-/-) cells or by ectopic expression of proteins that suppress p53 or c-Myc activity. Thus, DPP2 is essential for maintaining lymphocytes and fibroblasts in G(0), and its inhibition results in apoptosis mediated by induction of c-Myc and p53.
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PMID:Dipeptidyl peptidase 2 is an essential survival factor in the regulation of cell quiescence. 1971 73

Curcumin (diferuloylmethane) is the active ingredient of the spice plant Curcuma longa and has been shown to act anti-tumorigenic in different types of tumours. Therefore, we have studied its effect in pituitary tumour cell lines and adenomas. Proliferation of lactosomatotroph GH3 and somatotroph MtT/S rat pituitary cells as well as of corticotroph AtT20 mouse pituitary cells was inhibited by curcumin in monolayer cell culture and in colony formation assay in soft agar. Fluorescence-activated cell sorting (FACS) analysis demonstrated curcumin-induced cell cycle arrest at G2/M. Analysis of cell cycle proteins by immunoblotting showed reduction in cyclin D(1), cyclin-dependent kinase 4 and no change in p27(kip). FACS analysis with Annexin V-FITC/7-aminoactinomycin D staining demonstrated curcumin-induced early apoptosis after 3, 6, 12 and 24 h treatment and nearly no necrosis. Induction of DNA fragmentation, reduction of Bcl-2 and enhancement of cleaved caspase-3 further confirmed induction of apoptosis by curcumin. Growth of GH3 tumours in athymic nude mice was suppressed by curcumin in vivo. In endocrine pituitary tumour cell lines, GH, ACTH and prolactin production were inhibited by curcumin. Studies in 25 human pituitary adenoma cell cultures have confirmed the anti-tumorigenic and hormone-suppressive effects of curcumin. Altogether, the results described in this report suggest this natural compound as a good candidate for therapeutic use on pituitary tumours.
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PMID:Curcumin acts as anti-tumorigenic and hormone-suppressive agent in murine and human pituitary tumour cells in vitro and in vivo. 1972 38

We investigated the antiproliferative effects of synthetic flavanone derivatives using an MTT assay in MCF-7 and MDA-MB-453 cells. When cells were treated with synthetic flavanone derivatives in concentrations ranging from 1 to 200 microM for 48 h, cell growth decreased at concentrations >50 microM. 4'-Chloroflavanone is more potent than flavanone among the synthetic flavanone derivatives. Exposure to 4'-chloroflavanone at 50 microM for 48 h caused cell cycle arrest in both MCF-7 and MDA-MB-453 cells. In addition, when 4'-chloroflavanone caused G1/S phase arrest, a decrease in CDK4 and cyclin D, together with an increase in p21Cip1, was observed in the cells. The p21Cip1 is a downstream target of p53 that may be affected by the activation of p53 by 4'-chloroflavanone. These results indicate that activation of p53 played some role in 4'-chloroflavanone-induced cell cycle arrest of human breast cancer cells. 4'-Chloroflavanone increased cytochrome c expression and decreased the expression of caspase-3, but did not change the expression of Bcl-2 and Bax. Activation of cytochrome c and its downstream target, caspase-3, is suggested to be an important inducer of the apoptosis process by 4'-chloroflavanone. 4'-Chloroflavanone inhibits cell proliferation through G1/S phase disruption and may induce apoptosis. Based on our findings, we propose that 4'-chloro-flavanone is useful as an anticancer drug.
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PMID:Anti-carcinogenic effect of a new analogue 4'-chloroflavanone from flavanone in human breast cancer cells. 2004 41

MicroRNAs (miRNAs) are a class of endogenous small noncoding RNAs that regulate gene expression after transcription. Aberrant expression of miRNAs has been shown to be involved in tumorigenesis. We showed that miR-21 was one of the most frequently overexpressed miRNA in human glioblastoma (GBM) cell lines. To explore whether miR-21 can serve as a therapeutic target for glioblastoma, we downregulated miR-21 with a specific antisense oligonucleotide and found that apoptosis was induced and cell-cycle progression was inhibited in vitro in U251 (PTEN mutant) and LN229 (PTEN wild-type) GBM cells; xenograft tumors from antisense-treated U251 cells were suppressed in vivo. Antisense-miR-21-treated cells showed a decreased expression of EGFR, activated Akt, cyclin D, and Bcl-2. Although miR-21 is known to regulate PTEN and downregulation of miR-21 led to increased PTEN expression both endogenously and in a reporter gene assay, the GBM suppressor effect of antisense-miR-21 is most likely independent of PTEN regulation because U251 has mutant PTEN. Microarray analysis showed that the knockdown of miR-21 significantly altered expression of 169 genes involved in nine cell-cycle and signaling pathways. Taken together, our studies provide evidence that miR-21 may serve as a novel therapeutic target for malignant gliomas independent of PTEN status.
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PMID:Downregulation of miR-21 inhibits EGFR pathway and suppresses the growth of human glioblastoma cells independent of PTEN status. 2004 43


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