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)

Hepatocyte growth factor, which is now known to be the same protein as scatter factor, induced oligonucleosomal fragmentation of nuclear DNA of Sarcoma 180 cells and increased the activity of caspase-3, a key component in control of the apoptotic cell death pathway to about 2.6 times that in control cells on 48 hr incubation, but did not increase the activity of caspase-1. Both HGF-induced DNA fragmentation and caspase-3 activity were completely inhibited by co-incubation with an inhibitor of caspase-3, Ac-DEVD-H. In contrast, HGF did not affect the expression of the apoptosis suppressors Bcl-2 and Bcl-x. These results indicate that HGF activates the apoptosis signaling pathway by increasing caspase-3 activity in Sarcoma 180 cells.
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PMID:Hepatocyte growth factor/scatter factor activates the apoptosis signaling pathway by increasing caspase-3 activity in sarcoma 180 cells. 953 10

The activation of cytoplasmic signal transduction pathways by a number of growth factors and their tyrosine-kinase receptors, including hepatocyte growth factor/scatter factor (HGF/SF) and its receptor c-met, exerts an inhibitory influence on apoptosis induced by ionizing radiation in vitro. The clinical relevance of the aforementioned ligand-receptor pair, of Bcl-xL, which is targeted by HGF/SF/c-met signaling, and of Bcl-2, was assessed by evaluating their predictive and prognostic impact in a cohort of 97 patients with radically irradiated squamous cell cancers of the oropharynx. Immunohistochemical expression of c-met and Bcl-xL was correlated with decreased rates of complete remission of the primary tumor in both the univariate (c-met: P = 0.01; Bcl-xL: P = 0.001) and multivariate analyses. Expression of c-met was, moreover, a significant and independent predictor of impaired local failure-free survival (P = 0.003), disease-free survival (P = 0.003) and overall survival (p = 0.001). Bcl-2 expression was, on the other hand, associated with a favorable outcome, in terms of both local failure-free survival (P = 0.01) and overall survival (P = 0.001). In accordance with in vitro data, c-met and Bcl-xL appear to be involved in the resistance of oropharyngeal cancers to ionizing radiation, and may therefore represent attractive targets for radiosensitization.
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PMID:Involvement of the hepatocyte growth factor/scatter factor receptor c-met and of Bcl-xL in the resistance of oropharyngeal cancer to ionizing radiation. 1124 29

Congenital obstructive nephropathy is a common disease affecting fetuses and young children. The kidney shows profound morphologic and functional changes. The physiologic developmental kidney program is disturbed in the most advanced cases, arguing for altered temporal/spatial expression of genes which control normal nephrogenesis. Major regulators of mesenchymal-epithelial transformation and collecting duct and tubular development such as WT1 and Sall1 are decreased with obstruction. Additional candidate genes include GDNF/cRET, LIM1 and Pax2. Excessive apoptosis is an undisputed mechanism in these processes, mediated by decreased expression of apoptosis inhibiting genes (Bcl-2, HGF, IGF, BMP7), and overexpression of pro-apoptotic genes like Bax and TGF-beta. Renin and AT2R implicated in renal vascular development are decreased. Numerous extracellular matrix genes including Matrilysin are altered. The emerging theories of the biology of congenital obstructive nephropathy suggest new targets for therapeutic interventions with profound implications for these children.
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PMID:Biology of congenital obstructive nephropathy. 1266 Apr 11

The biological activities of Moxa, used as moxibustion, have not been well documented. We investigated here Moxa smoke for its tumor-specific cytotoxicity, anti-HIV activity, radical intensity and radical scavenging activity, in comparison with previously published data of Moxa extract. Moxa smoke showed slightly higher cytotoxicity against human tumor cell lines (oral squamous cell carcinoma HSC-2, HSC-3, promyelocytic leukemia HL-60) than against normal oral cells (gingival fibroblast HGF, pulp cell HPC, periodontal ligament fibroblast HPLF), yielding a tumor specificity index of 1.29. Moxa smoke dose-dependently induced internucleosomal DNA fragmentation, activation of caspases 3, 8 and 9, and slightly modified the expression of apoptosis-related proteins (Bcl-2, Bad, Bax) in HL-60 cells, but to much lesser extents than attained by positive controls (UV irradiation, actinomycin D treatment). ESR spectroscopy showed that Moxa smoke generated semiquinone-type radicals under alkaline conditions, and scavenged O2(-), hydroxyl radical, singlet oxygen and NO. All Moxa smoke preparations showed no apparent anti-HIV activity. These data demonstrate the antitumor potential of Moxa smoke.
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PMID:Cytotoxicity and radical modulating activity of Moxa smoke. 1579 3

Thalidomide (THAL) is currently used as a novel drug in patients with chemotherapy resistant or relapsed multiple myeloma. THAL antitumor activity seems to be very complex, however the precise mechanisms of its action are still not fully understood. The aim of this study was to assess some of possible mechanisms of THAL action both in in vivo analysis of immune cells phenotype and in in vitro cultures with THAL. The study involved 30 patients with relapsed or chemotherapy refractory multiple myeloma who were qualified to THAL treatment. We assessed immunophenotype of malignant plasma cells and T lymphocytes in both peripheral blood (PB) and bone marrow (BM) samples taken before and after 4 and 8 weeks of THAL treatment. Before therapy cytokine secretion (VEGF, HGF, bFGF, TNF, IL-6 an sIL-6R) and Bcl-2 expression in PB and BM cell cultures with THAL were analyzed. We used flow cytometry technique and ELISA method. The clinical response to therapy was assessed after 4 and 8 weeks of treatment. We also investigated microvessel density (MVD) in bone marrow samples before the THAL treatment and after 6 months of therapy in the group of responding patients. In cell cultures with THAL we detected statistically significant lowering of analyzed cytokines concentration and the decrease in Bcl-2 expression by malignant plasma cells in BM and CD8(+) T lymphocytes in BM and PB. In the group of patients responding to therapy we observed the decrease in the number of myeloma cells and significant increase of CD4(+) and CD8(+) cells in both PB and BM samples. There was statistically significant increase of CD3(+)/CD69(+) cells in the course of therapy, while the percentage of CD3+/HLA-DR(+) cells was significantly lower after 8 weeks of therapy. We also detected lowering of MVD after THAL therapy in responders group. The obtained results demonstrate that THAL efficacy in MM is multidirected and included such mechanisms like down-regulation of proangiogenic cytokines, that could lead to lowering of MVD, induction of apoptosis and influence on malignant cells and T lymphocytes immunophenotype.
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PMID:The influence of thalidomide therapy on cytokine secretion, immunophenotype, BCL-2 expression and microvessel density in patients with resistant or relapsed multiple myeloma. 1580 Jul 17

Doxorubicin (adriamycin), an anthracycline antibiotic, showed higher cytotoxic activity against human tumor cell lines (oral squamous cell carcinoma HSC-2, HSC-3, submandibular gland carcinoma HSG, promyelocytic leukemia HL-60) than against normal human cells (gingival fibroblast HGF, pulp cell HPC, periodontal ligament fibroblast HPLF). Doxorubicin activated caspases 3, 8 and 9 in both HSC-2 and HL-60 cells, but induced internucleosomal DNA fragmentation only in HL-60 cells. Western blot analysis showed that doxorubicin did not significantly change the intracellular concentration of Bcl-2, Bax and Bad in HL-60 cells. Real-time PCR analysis showed that HPC cells expressed the highest amount of mdr1 mRNA, followed by HSC-2 > HGF > HSC-3 > HPLF > HSG > HL-60. ESR spectroscopy showed that doxorubicin produced no discernible radical under alkaline conditions (pH 7.4 to 10.5) except at pH 12.5, and it did not scavenge O2-, NO and DPPH radicals. The present study demonstrates that doxorubicin induces the tumor-specific cytotoxicity and some, but not all, apoptosis markers possibly by a radical-independent mechanism, and that mdr1 expression in the tumor cells is not related to the tumor specificity of doxorubicin.
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PMID:Induction of tumor-specific cytotoxicity and apoptosis by doxorubicin. 1586 24

In search of compounds which show tumor-specific cytotoxic activity, two 3,5-dibenzoyl-1, 4-dihydropyridines (GB5, GB12) were found to show one or two orders higher cytotoxic activity against human tumor cell lines (squamous cell carcinoma HSC-2, HSC-3, submandibular gland carcinoma HSG, promyelocytic leukemia HL-60) than human normal cells (gingival fibroblast HGF, pulp cells HPC, periodontal ligament fibroblasts HPLF). GB5 and GB12 weakly induced several apoptosis-associated properties, such as internucleosomal DNA fragmentation, and activation of caspases -3, -8 and -9, in both HL-60 and HSC-2 cells. Western blot analysis showed that GB5 and GB12 transiently increased the expression of both anti-apoptotic protein (Bcl-2) and proapoptotic proteins (Bax and Bad) in HL-60 cells. ESR spectroscopy showed these compounds did not produce any detectable amount of radicals, nor scavenged superoxide (generated by hypoxanthine-xanthine oxidase reaction) or nitric oxide (generated by 1-hydroxy-2-oxo-3-(N-3-methyl-3-aminopropyl)-3-methyl-1-triazene), suggesting that the induction of cytotoxic action is not via a radical-mediated reaction. The present study suggests that GB5 and GB12 may induce non-apoptotic cell death in tumor cell lines.
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PMID:Tumor-specific cytotoxicity of 3,5-dibenzoyl-1,4-dihydropyridines. 1615 41

A total of eleven stilbenes [1-6] and flavonoids [7-11] were investigated for their tumor- specific cytotoxicity and apoptosis-inducing activity, using four human tumor cell lines (squamous cell carcinoma HSC-2, HSC-3, submandibular gland carcinoma HSG and promyelocytic leukemia HL-60) and three normal human oral cells (gingival fibroblast HGF, pulp cell HPC, periodontal ligament fibroblast HPLF). All of the compounds, especially sophorastilbene A [1], (+)-alpha-viniferin [2], piceatannol [5], quercetin [9] and isoliquiritigenin [10], showed higher cytotoxicity against the tumor cell lines than normal cells, yielding tumor-specific indices of 3.6, 4.7, >3.5, >3.3 and 4.0, respectively. Among the seven cell lines, HSC-2 and HL-60 cells were the most sensitive to the cytotoxic action of these compounds. Sophorastilbene A [1], piceatannol [5], quercetin [9] and isoliquiritigenin [10] induced internucleosomal DNA fragmentation and activation of caspases -3, -8 and -9 dose-dependently in HL-60 cells. (+)-alpha-Viniferin [2] showed similar activity, but only at higher concentrations. All the compounds failed to induce DNA fragmentation and activated caspases to much lesser extents in HSC-2 cells. Western blot analysis showed that sophorastilbene A [1], piceatannol [5] and quercetin [9] did not induce any consistent changes in the expression of pro-apoptotic proteins (Bax, Bad) and antiapoptotic protein (Bcl-2) in HL-60 and HSC-2 cells. An undetectable expression of Bcl-2 protein in control and drug-treated HSC-2 cells may explain the relatively higher sensitivity of this cell line to stilbenes and flavonoids.
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PMID:Tumor-specificity and apoptosis-inducing activity of stilbenes and flavonoids. 1615 45

Berberine iodide (IK-1) and acetoneberberine (IK-2) showed higher cytotoxicity against five human oral squamous cell carcinoma (HSC-2, HSC-3, HSC-4, NA, CA9-22) and one human promyelocytic leukemia (HL-60) cell lines, than against normal human oral tissue-derived cells (gingival fibroblast HGF, pulp cell HPC, periodontal ligament fibroblast HPLF), producing a tumor specificity index of 4.0 and 3.6, respectively. IK-1 was more potent than IK-2 in inducing the production of apoptotic cells, internucleosomal DNA fragmentation, the activation of caspases-3, -8 and -9, and the increased expression of proapoptotic BAD protein, with a corresponding decrease in the expression of anti-apoptotic Bcl-2 protein in HL-60 cells. These compounds did not induce internucleosomal DNA fragmentation (only producing larger DNA fragment), nor increased the Bad protein expression in HSC-2 cells. The present study demonstrated the tumor-specific cytotoxicity and apoptosis-inducing activity of berberines, suggesting their possible antitumor potentiaL
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PMID:Tumor-specific cytotoxicity and apoptosis-inducing activity of berberines. 1630 99

HGF is a multifunctional polypeptide with mitogenic, motogenic and morphogenic effects. These effects are mediated by c-met, a specific receptor of HGF and a member of the receptor tyrosine kinase superfamily, virtually expressed in every type of kidney cell. HGF has a central role during embryogenesis since it stimulates epithelial differentiation of metanephric mesenchymal cells and induces branching tubules, as experiments in epithelial cells cultures demonstrated. Several studies have shown also that HGF accelerates the recovery from toxic-ischemic acute renal failure. This effect seems to be mediated by the inhibition of programmed cell death and an increased cell survival. HGF inhibits apoptosis by upregulating the protooncogene Bcl-2 and downregulating Bax. Since HGF can modulate extracellular matrix turnover, authors suggest its beneficial role in tissue remodelling and particularly in chronic renal diseases. Several studies reported a key role for HGF in reducing interstitial fibrosis and glomerular sclerosis, both in in vivo and in vitro models. This protective effect is secondary to HGF antagonizing the profibrotic action of TGF-beta. HGF modulates the balance between synthesis and degradation of extracellular matrix, increasing the expression of metalloproteases and reducing the production of their specific inhibitors TIMPs. Furthermore HGF suppresses the effect of TGF-beta by blocking the axis TGF-beta/Smad. Last, the antifibrotic effect of HGF might be modulated by the proliferative status of target cells. To sum up, the supplementation of exogenous HGF or the induction of endogenous HGF expression may provide an effective therapeutic strategy for combating chronic renal diseases.
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PMID:[Hepatocyte growth factor and kidney]. 1706 38


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