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)

The biological function of GFPPS1b, a novel polysaccharide-peptide isolated from cultured mycelia of Grifola frondosa GF9801, was well investigated. GFPS1b has anti-tumor activity and can significantly inhibit the proliferation of SGC-7901 cells, whereas slightly influences the growth of human normal liver cell line L-02. When treated with GFPS1b, SGC-7901 cells showed typical apoptotic morphological features such as the loss of villus and appearance of apoptotic bodies on the cell surface, volume reduction, and chromatin condensation, by scanning electron microscopy (SEM) and fluorescent microscopy (Hoechst 33342). The results of flow cytometry analysis and annexin V-PI assay showed that the SGC-7901 cell cycle was arrested in the G(2)/M phase, the subdiploid peak of DNA characteristic of apoptotic was also observed, and the apoptosis ratio was about 15.08%. DNA isolated from SGC-7901 cells cultured with GFPS1b showed a typical DNA 'ladders' of apoptosis in agarose gel electrophoresis. Further investigation results showed that the apoptotic machinery of SGC-7901 induced by GFPS1b was associated with drop in mitochondrial trans-membrane potential, upregulation of Bax, downregulation of Bcl-2, and activation of caspase-3. Our finding suggests that GFPS1b could suppress SGC-7901 cell growth and reduce cell survival via arresting cell cycle and inducing apoptosis of tumor cells.
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PMID:Induction of apoptosis in SGC-7901 cells by polysaccharide-peptide GFPS1b from the cultured mycelia of Grifola frondosa GF9801. 1715 Mar 27

Nephrotic-range proteinuria is considered a poor prognostic factor. A correlation between tubulointerstitial injury and the degree of proteinuria is well established. In an attempt to explain the tubular atrophy that is observed in advanced glomerulonephritides, this study investigated apoptotic mechanisms in cultured human proximal tubule cells (HKC-8) that were exposed to endotoxin-free albumin (5, 10, and 20 mg/ml). Apoptosis was detected by Hoechst 33342; annexin staining; and assays for caspases 3, 8, and 9. The apoptotic effect of albumin was maximal at 10 mg/ml albumin, and necrosis prevailed in cells that were incubated with 20 mg/ml. Increase in caspase-9 and -3 activity was observed starting at 6 and maximally at 16 to 24 h. The proapoptotic Bcl-2 protein Bax was upregulated at 6 h, associated with translocation of cytochrome-c from mitochondria to cytosol and alteration in the mitochondrial membrane potential. Production of reactive oxygen species (ROS) was significant at 6 h but declined at 16 and 24 h. Treatment with ROS scavenger dimethylthiourea or antioxidant N-acetylcysteine did not alleviate caspase-3 production. Pan protein kinase C inhibitor bisindolylmaleimide-1 protected the cells from apoptosis. It is concluded that albumin induces apoptosis in human proximal tubule cells by stimulating mitochondrial apoptotic pathway independent of ROS production.
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PMID:Mitochondria are the major targets in albumin-induced apoptosis in proximal tubule cells. 1736 Sep 44

Cancer stem cells are supposed to be resistant to apoptosis, but information for this is quite limited. Cancer stem cells are usually isolated as dye-effluxing cells with Hoechst 33342 staining, called side-population (SP) cells. Because Hoechst 33342 dye itself induces apoptosis, the SP cells isolated by such method are not suitable for evaluation of apoptosis. For accurate assessment, SP cells must be isolated without Hoechst 33342. Here, we found that CD55 was highly expressed in SP cells of two mammary gland carcinoma cell lines. Then, the high expression of CD55 was used for isolation of cancer stem cells among mammary carcinoma cell lines as a surrogate character. Cells expressing high level of CD55 (CD55(hi)) were resistant to apoptosis induced by serum depletion as in the case of SP cells. In ceramide-inducing apoptosis, CD55(hi) cells showed high tolerance. Anti-apoptotic molecules such as Bcl-2 were abundantly expressed in both SP cells and CD55(hi) cells. These findings indicated that SP cells as revealed to be CD55(hi) cells were tolerant to apoptosis. The high expression of CD55 may be a useful character for SP cells in evaluating their functions.
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PMID:High tolerance to apoptotic stimuli induced by serum depletion and ceramide in side-population cells: high expression of CD55 as a novel character for side-population. 1742 72

The present study was designed to assess the effect of matrine, an active component of Chinese traditional medicine, on angiotensin II (Ang II)-induced hyperplastic growth of cardiac fibroblasts in vitro. Cardiac fibroblasts were prepared from hearts of neonatal Kunming mice by collagenase disruption. Cultured cardiac fibroblasts were either not treated, treated with 0.1 microM Ang II, or matrine (2.0 approximately 4.0 mM) plus Ang II for 12-72 hr. Cell morphology was monitored under an inverted phase contrast microscope. Number of cells was counted with a haemocytometer. Cell apoptosis was determined by propidium iodide/Hoechst 33342 staining and flow cytometry. The cleaved caspase-3 fragment expression, anti-apoptotic Bcl-2 and pro-apoptotic Bax protein expressions were also studied. The results show that Ang II stimulation resulted in hyperplastic growth of cardiac fibroblasts. Matrine significantly, dose and time dependently inhibited Ang II-induced cell proliferation. Matrine addition to the culture medium led to most cells being arrested in the G1 phase of the cell cycle, the fraction of cells in S phase was markedly decreased compared to control and Ang II alone groups. Cell apoptosis in matrine treatment group was markedly increased, accompanied by down-regulation in Bcl-2/Bax ratio and up-regulation in cleaved caspase-3 activity. These results suggest that matrine can induce apoptosis and thereby inhibit Ang II-induced hyperplasic growth of cardiac fibroblasts. The regulations of matrine on Bcl-2/Bax expression and caspase-3 activation may be the pro-apoptotic mechanisms involved.
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PMID:Matrine induces apoptosis in angiotensin II-stimulated hyperplasia of cardiac fibroblasts: effects on Bcl-2/Bax expression and caspase-3 activation. 1757 9

Curcumin, a major pigment of turmeric, is a natural antioxidant possessing a variety of pharmacological activities and therapeutic properties. But its mechanisms are unknown. In our previous study, we found that a 2-h exposure to curcumin induced DNA damage to both the mitochondrial DNA (mtDNA) and the nuclear DNA (nDNA) in HepG2 cells and that mtDNA damage was more extensive than nDNA damage. Therefore, experiments were initiated to evaluate the role of mtDNA damage in curcumin-induced apoptosis. The results demonstrated that HepG2 cells challenged with curcumin for 1 h showed a transient elevation of the mitochondrial membrane potential (DeltaPsim), followed by cytochrome c release into the cytosol and disruption of DeltaPsim after 6 h exposure to curcumin. Apoptosis was detected by Hoechst 33342 and annexin V/PI assay after 10 h treatment. Interestingly, the expression of Bcl-2 remained unchanged. A resistance to apoptosis for the corresponding rho0 counterparts confirmed a critical dependency for mitochondria during the induction of apoptosis in HepG2 cells mediated by curcumin. The effects of PEG-SOD in protecting against curcumin-induced cytotoxicity suggest that curcumin-induced cytotoxicity is directly dependent on superoxide anion O2- production. These data suggest that mitochondrial hyperpolarization is a prerequisite for curcumin-induced apoptosis and that mtDNA damage is the initial event triggering a chain of events leading to apoptosis in HepG2 cells.
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PMID:Curcumin induces apoptosis through mitochondrial hyperpolarization and mtDNA damage in human hepatoma G2 cells. 1769 41

To determine the effects of cobalt chloride on human submandibular gland cells, HSG cells were exposed to various concentrations of cobalt chloride. Cobalt chloride induced cytotoxicity and cell death in HSG cells as determined by phase-contrast microscopy and WST-1 cell viability assay. By using the Hoechst 33342 staining, marked nuclear condensation and fragmentation of chromatin were observed in cobalt chloride-treated cells. Cobalt chloride induced DNA ladder formation in HSG cells in both dose- and time-dependent manner with maximal effect at a concentration of 0.5 mM and 48 h, respectively. Cobalt chloride inhibited the expression of both Bcl-2 protein and mRNA in dose- and time-dependent manner. Zinc chloride recovered the cobalt-suppressed Bcl-2 expression and protected against cobalt-induced apoptosis in HSG cells. Our results show that the pathway of the apoptosis in HSG cells is regulated by cobalt chloride and zinc chloride. Our results also indicate that cobalt-induced apoptotic steps in HSG cells are related to the production of Bcl-2 protein.
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PMID:Cobalt chloride induces apoptosis and zinc chloride suppresses cobalt-induced apoptosis by Bcl-2 expression in human submandibular gland HSG cells. 1778 26

Eupalinin A, a natural phytoalexin included in Eupatorium chinense L., exhibited a marked inhibitory effect on cell growth in HL60 cells. The morphological aspects of eupalinin A-treated cells evaluated by Hoechst 33342 nuclear staining indicated cell death, only a small part of which showed a typical apoptosis with nuclear fragmentation and condensation. To determine what type of cell death is caused by eupalinin A, we examined the contribution of caspases, Bcl-2 family proteins, MAP kinase, and PI3K/Akt, and mitochondrial membrane potential to this cell death. As a result, most part of the cell death was not associated with apoptosis because of caspase independence and no death factor released from mitochondria. Electron microscopic study indicated a characteristic finding of autophagy such as the formation of autophagosomes. Furthermore, the level of microctubule-associated-protein light chain 3 (LC3) II protein and monodancylcanaverin (MDC) incorporation were gradually increased with reduction of mitochondrial membrane potential by the accumulation of intracellular ROS after eupalinin A treatment. From these results, we can conclude that eupalinin A-induced cell death was mainly due to autophagy, which was initiated by increased ROS, resulting in the perturbation of mitochondrial membrane potential. Since the class III PI3K inhibitor such as 3-MA or LY294002 did not inhibit the eupalinin A-induced type II programmed cell death (PCD II), it was suggested that the PCD II was executed by Beclin-1 independent pathway of damage-induced mitochondrial autophagy (mitophagy).
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PMID:Eupalinin A isolated from Eupatorium chinense L. induces autophagocytosis in human leukemia HL60 cells. 1798 Jun 7

We have investigated the antiproliferative effects of TBIDOM (N-(4-(2,2,2-trifluoroethyl) benzylidene) (7-isopropyl-1,4a-dimethyl-1,2,3,4,4a,9,10,10a-octahydrophenanthren-1-yl) meth-anamine) and have explored its possible mechanisms on human hepatocellular carcinoma SMMC-7721 cells. The proliferative status of cells treated with TBIDOM was measured by the colorimetric MTT assay. Cellular apoptosis was analysed using Hoechst 33342 staining and flow cytometry. Reduction of mitochondrial membrane potential (Delta psi(m)) was also detected by flow cytometry. Western blotting assay was used to evaluate the release of cytochrome c and expression of p53, Bcl-2 and Bax proteins. It was shown that TBIDOM displayed a significant inhibitory effect on growth of SMMC-7721 cells in a dose- and time-dependent manner. Hoechst 33342 staining and flow cytometry analysis showed an increase of apoptosis rate and decrease of mitochondrial membrane potential after SMMC-7721 cells were exposed to TBIDOM for 24 h. Pretreatment of SMMC-7721 cells with TBIDOM significantly induced a decrease of Bcl-2 protein expression and an increase of caspase-3 activity and Bax protein expression. The results indicated that TBIDOM could effectively inhibit proliferation by induction of apoptosis and could be a promising candidate in the development of a novel class of antitumour agent.
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PMID:Cytotoxic effects and pro-apoptotic mechanism of TBIDOM, a novel dehydroabietylamine derivative, on human hepatocellular carcinoma SMMC-7721 cells. 1823 68

The expression of growth hormone-releasing hormone (GHRH) and its receptors has been demonstrated in peripheral tissues as well as CNS. Recently, the functional splice variant SV1 of GHRH receptor was identified in various human cancers and cancer cell lines. Although antineoplastic activity of GHRH antagonists has been clearly demonstrated, the mechanism of action is incompletely understood. The objective of this study was the investigation of direct anti-proliferative effect of GHRH antagonist MZ-5-156 on HEC-1A human endometrial cancer cell line and the elucidation of underlying mechanisms. RT-PCR revealed the expression of mRNA for GHRH and SV1 of GHRH receptor in HEC-1A cells. MZ-5-156, at concentrations between 10(-7) and 10(-5) M, had a dose-dependent antiproliferative effect on HEC-1A cells, as determined by 3-(4,5-dimethylthiazol-2-yl)-5-(3-carboxymethoxyphenyl)-2-(4-sulfophenyl)-2H-tetrazolium, (MTS) assay. Hoechst 33342 staining and flow cytometric analysis indicated that MZ-5-156, at 10(-6) M, induced apoptosis in HEC-1A cells after 48 h of treatment. Western blot analysis of apoptosis-related proteins demonstrated that treatment with MZ-5-156 (10(-6) M) for 48 h significantly increased the protein levels of Fas, phospho-p53 (Ser46), p53AIP1 (p53-regulated Apoptosis-Inducing Protein 1), and caspase-8, -9, and -3, and decreased the protein level of Bcl-2. These results demonstrate that MZ-5-156 can directly inhibit the proliferation of human endometrial cancer cells, which express mRNA for GHRH and SV1 of GHRH receptor, presumably through the induction of p53-dependent apoptosis coupled with the up-regulation of Fas, phospho-p53 (Ser46), p53AIP1, and caspase-8, -9, and -3, and the down-regulation of Bcl-2.
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PMID:Cellular mechanisms of growth inhibition of human endometrial cancer cell line by an antagonist of growth hormone-releasing hormone. 1829 36

Olfactory ensheathing cells (OECs) express a high level of growth factors which play a very important role as neuronal support. Recent evidence in literatures showed that transplantation of OECs may improve functional restoration in 6-OHDA-induced rat model of Parkinson's disease (PD). However, the biological function of various factors released from OECs in Parkinson' disease is still unclear. In this study, we examined the effects of newborn rat OECs conditioned medium (CM) on PC12 cells. Cells treated with 6-OHDA underwent cytotoxicity and apoptotic death determined by MTT assay and Hoechst 33342/PI staining. OECs CM was able to reduce the cellular damage in PC12 cells. Further investigation results showed that CM inhibited the disruption of mitochondrial transmembrane potential, up-regulation of Bcl-2 and down-regulation of Bax. Taken together, this study indicates that CM has a neuroprotective effect on 6-OHDA induced apoptosis of PC12 cells, which is through up-regulation of the Bcl-2/Bax ratio and protection for mitochondrion.
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PMID:Olfactory ensheathing cells conditioned medium prevented apoptosis induced by 6-OHDA in PC12 cells through modulation of intrinsic apoptotic pathways. 1829 31


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