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)

Depletion of calcium from the neuronal endoplasmic reticulum (ER) induces apoptosis. Isoflurane depletes calcium from sarcoplasmic reticulum (SR) of muscle, an analogue of ER in neurons, while sevoflurane maintains or increases SR calcium. We hypothesized that isoflurane, but not sevoflurane, induces apoptosis by depleting the ER calcium. Rat PC12 pheochromocytoma cells and primary cortical neurons were treated with equipotent doses of isoflurane and sevoflurane. Isoflurane, but not sevoflurane, at equipotent doses induced cell damage determined by both LDH release and MTT reduction assays, dose and time dependently, in both types of cells. Isoflurane at 2.4% for 24 h induced cytotoxicity in both cell types, which was characterized by nuclear condensation and fragmentation and activation of caspases 3 and 9. Isoflurane cytotoxicity was suppressed by dantrolene, a ryanodine receptor antagonist that inhibits abnormal calcium release from the ER. Isoflurane decreased the Bcl-2/Bax ratio by as much as 36% (P < 0.05). However, sevoflurane did not cause neuronal damage by apoptosis nor did it decrease the Bcl-2/Bax ratio. These results suggest that isoflurane and sevoflurane differentially affect the Bcl-2/Bax ratio and cell survival. At equipotent concentrations, isoflurane, but not sevoflurane, induces cytotoxicity in both PC12 cells and primary cortical neurons and decreases the Bcl-2/Bax ratio.
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PMID:Isoflurane and sevoflurane affect cell survival and BCL-2/BAX ratio differently. 1577 62

It is known that liquorice root is rich in compounds which exert several pharmacological actions. In the present study, we evaluated the effect of glycyrrhizin (the main constituent of liquorice root) and of its metabolite aglycone, 18beta-glycyrrhetinic acid, on UVB-irradiated human melanoma cells: SKMEL-2 from metastatic tissue and SKMEL-28 from primary malignant melanoma. Tests performed (Trypan blue exclusion test, MTT and Western blot) showed that glycyrrhizin is not toxic for both types of cells. In SKMEL-28 cells, Bcl-2 expression was low after UVB irradiation, but it was increased when treated with glycyrrhizin. On the contrary, in the SKMEL-2 cell culture, Bcl-2 expression was not modified by the substances under study. The results show that glycyrrhizin treatment might offer protection from the damage induced in humans by UVB radiation, while it seems to be ineffective on metastatic cells. Further studies must be performed to understand the mechanism of the protective effect.
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PMID:Effects of glycyrrhizin on UVB-irradiated melanoma cells. 1579 92

The nuclear receptors PPARs (peroxisome proliferator-activated receptors) are transcription factors activated by specific ligands. PPARs play an important role in carcinogenesis, inflammation, atherosclerosis, lipid metabolism and diabetes. There is evidence that activation of PPARs by specific ligands is able to suppress the growth of different types of human cancer by mechanisms including the growth arrest, apoptosis and induction of differentiation, although the detailed signalling pathways have not been completely elucidated to date. The aim of our study was to determine whether synthetic ligands of PPARalpha and PPARgamma could affect the viability, proliferation, differentiation, apoptosis and expression of some cell cycle related proteins in glial tumor cell lines. The study was performed on human glioblastoma cell lines U-87 MG, T98G, A172 and U-118 MG. Cell lines were treated by ligands of PPARalpha (bezafibrate, gemfibrozil) and PPARgamma (ciglitazone). MTT, flow cytometry, TUNEL assay and immunoblotting were used for detection of changes in cell viability, proliferation, differentiation and apoptosis. Bezafibrate, ciglitazone and gemfibrozil inhibited viability of glioblastoma cell lines. The synthetic ligands significantly reduced or induced the expression of cyclins, p27Kip1, p21Waf1/Cip1, MDM-2, Bcl-2, Bax, PARP, Caspase 3, androgen receptors, etc. and did not affect the expression of the differentiation marker GFAP. Flow cytometry confirmed arrest of the cell cycle although the detection of apoptosis was controversial. Apart from hypolipidemic and hypoglycaemic effects, PPAR ligands may also have significant cytostatic effects of potential use in anticancer treatment.
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PMID:Peroxisome proliferator-activated receptors (PPAR) agonists affect cell viability, apoptosis and expression of cell cycle related proteins in cell lines of glial brain tumors. 1580 Jul 11

Beta-lapachone, the product of a tree Tabebuia avellanedae from South America, is known to exhibit various pharmacologic properties, the mechanisms of which are poorly understood. In the present study, we investigated further possible mechanisms by which beta-lapachone exerts its anti-proliferative action in cultured human prostate carcinoma DU145 cells. Exposure of DU145 cells to beta-lapachone resulted in growth inhibition and induction of apoptosis in a dose-dependent manner as measured by MTT assay, fluorescent microscopy, and flow-cytometry analysis. The increase in apoptosis was associated with a dose-dependent up-regulation in pro-apoptotic Bax expression, down-regulation of anti-apoptotic Bcl-2, and proteolytic activation of caspase-3 protease. We found beta-lapachone decreased the levels of cyclooxygenase (COX)-2 mRNA and protein expression without significant changes in the levels of COX-1, which was correlated with a decrease in prostaglandin E2 (PGE2) synthesis. Furthermore, beta-lapachone treatment markedly inhibited the activity of telomerase in a dose-dependent fashion. Additionally, the expression of human telomerase reverse transcriptase (hTERT), a main determinant of the telomerase enzymatic activity, was progressively down-regulated by beta-lapachone treatment. Taken together, these findings provide important new insights into the possible molecular mechanisms of the anti-cancer activity of beta-lapachone.
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PMID:Down-regulation of cyclooxygenase-2 and telomerase activity by beta-lapachone in human prostate carcinoma cells. 1582 36

The induction of apoptosis and antiproliferation effect of cytokine-induced killer cells (CIK cells) on MGC- 803 cells and its mechanisms were studied by using a tetrazolium dye-based (MTT) assay. Morphological changes were observed by using inverted microscope, haematoxylin/eosin (HE) staining, scanning electron microscope, and transmission electron microscope. The TdT-mediated dUTP nick and labeling (TUNEL) method was used to detect the apoptosis-induced by CIK cells. The expression rate of p53, p16, C-myc, Bcl-2, and Bax proteins were studied by using immunohistochemical staining. There were significant differences according to varied effector-target ratios at the same working time (p < 0.01) and the same effector-target ratios at different working times (p < 0.01). Inverted microscope and HE staining observation showed that CIK cells were closer to the target cells and formed a typical "rose" shape. The scanning electron microscope showed that most target cells had undergone apoptosis and many "apoptotic bodies," and that transmission electron microscopy showed condensed chromatin, disintegration of the nucleolus, vacuoles in the cytoplasm, and apoptotic bodies appearing in most target cells. TUNEL analysis showed that apoptotic cells contract and turn navy blue in nuclei or perinuclei in the experimental group. The apoptotic rate was upmodulated between 5 and 14 hours and downregulated between 14 and 24 hours in the "CIK" experimental group. The expression of p53, p16, C-myc, and Bcl-2 were significantly downregulated (p < 0.01), and the expression of Bax was upregulated over the time of coculture in the "CIK" experimental group, compared to the control group. Our studies suggested that CIK cells induce apoptosis and have an antiproliferative effect on human MGC-803 gastric cancer cells. The CIK cells kill MGC-803 gastric cancer cells by inducing apoptosis in the early stage and by inducing necrosis in the late stage through the downregulating expression of p53, C-myc, and Bcl-2 and the upregulating expression of Bax.
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PMID:Studies on inducing apoptosis effects and mechanism of CIK cells for MGC-803 gastric cancer cell lines. 1586 51

Coriolus versicolor (CV), also called Yunzhi, has been demonstrated to exert anti-tumor effects on various types of cancer cells, but the underlying mechanism has not been fully elucidated. The present study aimed to evaluate the in vitro anti-tumor activity of a standardized aqueous ethanol extract prepared from CV on four breast cancer cell lines using MTT assay, and test whether the mechanism involves apoptosis induction and modulation of p53 and Bcl-2 protein expressions using cell death detection ELISA, p53 and Bcl-2 ELISAs respectively. Our results demonstrated that the CV extract dose-dependently suppressed the proliferation of three breast tumor cell lines, with ascending order of IC50 values: T-47D, MCF-7, MDA-MB-231, while BT-20 cells were not significantly affected. Tumoricidal activity of the CV extract was found to be comparable to a chemotherapeutic anti-cancer drug, mitomycin C. Nucleosome productions in apoptotic MDA-MB-231, MCF-7 and T-47D cells were significantly augmented in a time-dependent manner and paralleled the anti-proliferative activity of CV extract. Expression of p53 protein was significantly upregulated only in T-47D cells treated with the CV extract in a dose- and time-dependent fashion, but not in MCF-7 (except at 400 mug/ml after 16 h) and MDA-MB-231 cells. The CV extract significantly induced a dose-dependent downregulation of Bcl-2 protein expression in MCF-7 and T-47D cells, but not in MDA-MB-231 cells. These results suggested that apoptosis induction, differentially dependent of p53 and Bcl-2 expressions, might be the possible mechanism of CV extract-mediated cytotoxicity in human breast cancer cells in vitro.
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PMID:Differential anti-tumor activity of coriolus versicolor (Yunzhi) extract through p53- and/or Bcl-2-dependent apoptotic pathway in human breast cancer cells. 1590 82

Celecoxib, a selective cyclooxygenase-2 (COX-2) inhibitor, is the only non-steroidal anti-inflammatory drug so far which has been approved by the FDA for adjuvant treatment of patients with familial adenomatous polyposis. The molecular mechanism responsible for the anti-cancer effects of celecoxib is not fully understood. There is little data on the potential role of COX-2 in lymphoma pathogenesis. In view of the reported induction of apoptosis in cancer cells by cyclooxygenase-2 inhibitors, the present study is undertaken to test the effect of celecoxib on human chronic myeloid leukemia cell line, K562 and other hematopoietic cancer cell lines like Jurkat (human T lymphocytes), HL60 (human promyelocytic leukemia) and U937 (human macrophage). Treatment of these cells with celecoxib (10-100 microM) dose-dependently, reduced cell growth with arrest of the cell cycle at G0/G1 phase and induction of apoptosis. Further mechanism of apoptosis induction was elucidated in detail in K562 cell line. Apoptosis was mediated by release of cytochrome c into the cytoplasm and cleavage of poly (ADP-ribose) polymerase-1 (PARP-1). This was followed by DNA fragmentation. The level of anti-apoptotic protein Bcl-2 was decreased without any change in the pro-apoptotic Bax. Celecoxib also inhibited NF-kB activation. Celecoxib thus potentiates apoptosis as shown by MTT assay, cytochrome c leakage, PARP cleavage, DNA fragmentation, Bcl-2 downregulation and possibly by inhibiting NF-kB activation.
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PMID:Anti-proliferative and apoptotic effects of celecoxib on human chronic myeloid leukemia in vitro. 1591 Oct 99

PANcreatic DERived factor (PANDER, FAM3B) is a recently discovered islet-specific cytokine. We have previously shown that, in vitro, truncated recombinant PANDER isoforms (20 and 21 kDa) are cytotoxic to beta-cell lines but the effects of full-length PANDER on islet biology remain unclear. In this study, we used adenovirus (Ad-PANDER) to overexpress full-length cDNA of PANDER in islets and betaTC3 cells. BetaTC3 cells were infected with Ad-PANDER or control vector. After 48 h, cell viability was significantly decreased as evaluated by MTT assay. The number of dead cells was significantly increased as indicated by the fluorescent intensity of the propidium iodide-stained cells (160 +/- 13 vs. control 100 +/- 7%, P = 0.001). Flow cytometric Tunel assay showed that overexpressing PANDER induced a significant fourfold increase in beta-cell apoptosis (19.4 +/- 6.3 vs. control 4.1 +/- 0.8%, P < 0.05). There was a significant increase in the number of annexin V-positive (apoptotic) cells and propidium iodide-positive (dead) cells in mouse islets infected with Ad-PANDER compared with control cells infected with Ad-LacZ. Addition of 4 nM recombinant PANDER protein to betaTC3 cells or infection of Ad-PANDER did not affect Akt and STAT1 phosphorylation, Bcl-2, Fas, and NF-kappaB protein levels. However, activation of caspase-3 was observed in betaTC3 and islets infected with Ad-PANDER. Overexpression of PANDER in mouse islets or addition of recombinant PANDER decreased insulin secretion induced by carbachol plus glucose or high potassium but not that by glucose alone. Culture with recombinant PANDER did not affect glucose-induced NAD(P)H elevation in mouse islets. In conclusion, Ad-PANDER infection is as effective as truncated recombinant PANDER to induce betaTC3 cell and mouse islet apoptosis.
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PMID:Effects of overexpression of pancreatic derived factor (FAM3B) in isolated mouse islets and insulin-secreting betaTC3 cells. 1592 25

Thallium acetate is a known neurotoxic agent. In this study, we investigated the mechanisms by which thallium acetate induces cell cycle arrest and cell apoptosis in cultured LC6 glioma cells. Exposure of C6 glioma cells to thallium acetate decreased cell viability as demonstrated by the MTT assay. Incubation of thallium acetate arrested cell cycle progression at the G2/M phase and caused cellular apoptosis at 300 microM as determined by trypan blue exclusion and flow cytometric analysis. The G2/M arrest was associated with a decrease in expression of CDK2 protein and an upregulation of p53 and the CDK inhibitor p21(Cip1), but not p27(Kip1). Thallium acetate did not alter the protein levels of cyclin A and B; cyclin D1, D2, and D3; and CDK4 expression in C6 glioma cells. Incubation of C6 glioma cells with thallium acetate upregulated the expression of proapoptotic proteins Bad and Apaf and downregulated the expression of anti-apoptotic proteins Bcl-xL and Bcl-2. In conclusion, these data suggest that thallium acetate inhibits cell cycle progression at G2/M phase by suppressing CDK activity through the p53-mediated induction of the CDK inhibitor p21(Cip1). Impairment of cell cycle progression may trigger the activation of a mitochondrial pathway and shifts the balance in the Bcl-2 family toward the proapoptotic members, promoting the formation of the apoptosome and, consequently, apoptosis.
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PMID:Thallium acetate induces C6 glioma cell apoptosis. 1596 99

FTY720, a derivative of fungus, has demonstrated dramatic anticancer effect in several malignancies recently. Our study evaluates the therapeutic potential of FTY720 in the treatment of androgen-independent prostate cancer using a human prostate cancer xenograft in nude mice. CWR22R, an androgen-independent human prostate tumor xenograft was inoculated into castrated nude mice and the animals were administrated with either normal saline or FTY720 (10 mg/kg) through intraperitoneal (i.p.) injection for 20 days. Body weight and tumor volume were recorded every 2 days, and serum prostate specific antigen (PSA) levels were also measured before and after the treatment. The effect of FTY720 on tumor cell proliferation was examined using antibodies against PCNA and Ki-67 by immunohistochemical staining, MTT assay and colony forming assay, whereas apoptotic effect of FTY720 was evaluated by TUNEL assay and immunostaining using antibodies against cleaved caspase 3 and Bcl-2. In addition, the potential inhibitory effect of FTY720 on prostate cancer angiogenesis and metastasis was investigated by immunostaining of CD31, VEGF, E-cadherin and beta-catenin. Our results showed that FTY720 treatment led to suppression of CWR22R tumor growth without causing any detectable side effects in nude mice. The FTY720-induced tumor suppression was correlated with decreased serum PSA level as well as reduced proliferation rate, suppression of angiogenic factors, and restoration of E-cadherin and beta-catenin expression. In addition, the FTY720-treated tumors showed increased apoptosis rate demonstrated by increased TUNEL- and cleaved caspase 3-positive cells, and decreased Bcl-2 expression. Our results suggest a potential novel agent in the suppression of androgen-independent prostate cancer.
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PMID:FTY720, a fungus metabolite, inhibits in vivo growth of androgen-independent prostate cancer. 1598 40


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