UNIPROT:P10415 - FACTA Search

Gene/Protein Disease Symptom Drug Enzyme Compound
Pivot Concepts: Target Concepts:

Query: UNIPROT:P10415 (Bcl-2)
33,771 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

Type I interferon (IFN) receptor consists of two chains (Hu-IFN-alphaR1 and Hu-IFN-alphaR2), and Hu-IFN-alphaR2 takes a soluble (Hu-IFN-alphaR2a), short (Hu-IFN-alphaR2b), or long (Hu-IFN-alphaR2c) form. We examined the expression of type I IFN receptor, the growth-suppression effect of IFN-alpha, and their relationship in 13 liver cancer cell lines. With reverse-transcription polymerase chain reaction (RT-PCR) analysis, the expressions of Hu-IFN-alphaR1, Hu-IFN-alphaR2a, and Hu-IFN-alphaR2c were confirmed in all cell lines, and that of Hu-IFN-alphaR2b in 12 cell lines. All cell lines expressed mRNAs of a transcriptional activator, interferon regulatory factor (IRF)-1, and its antagonistic repressor (IRF-2). Flow cytometry revealed weak expression of Hu-IFN-alphaR2 on the cell surface in 12 cell lines. The soluble-form protein of Hu-IFN-alphaR2 was detected at varying levels in culture supernatants of all cell lines with enzyme-linked immunosorbent assay (ELISA). Cell proliferation was suppressed in proportion to the dose of human natural IFN-alpha at 96 hours of culture, but it was not clearly related to the expression of Hu-IFN-alphaR2 protein on the cell surface. Investigations on the morphology, DNA, and cell cycle presented four growth suppression patterns as a result of IFN-alpha: 1) induction of apoptosis and blockage of cell cycle at the S phase (9 cell lines); 2) blockage at the S phase (2 cell lines); 3) induction of apoptosis and blockage at the G2/M phase (1 cell line); and 4) blockage at the G1 phase (1 cell line). There was no evidence showing that changes in the expressions of Bcl-2, Bcl-xL, Bak, and Bax lead directly to IFN-alpha-mediated apoptosis. Our findings demonstrated that IFN-alpha would express growth-suppression effects at varying degrees by inducing inhibition of cell-cycle progression with or without apoptosis, regardless of the expression level of Hu-IFN-alphaR2 protein on the cell surface.
...
PMID:Interferon alfa receptor expression and growth inhibition by interferon alfa in human liver cancer cell lines. 1034 12

Bcl-2 protein is one of the major apoptosis regulators. The study examines the effect of Bcl-2 protein on the chemosensitivity of a human hepatocellular carcinoma cell line, QGY-7703. Western blot analysis showed that Bcl-2 and Bax proteins were expressed in QGY-7703 cells. Characteristic features of Taxol- and doxorubicin-induced apoptosis were evidenced by the Annexin-V binding assay, TUNEL and DAPI staining. At constant Bax protein levels, stable sense and antisense gene-transfected QGY-7703 cells showed that constitutive expression of Bcl-2 could render the cells more resistant to Taxol and doxorubicin. Contrarily, decreased Bcl-2 levels caused the cells to be more sensitive to the drugs. As Bcl-2 levels are directly proportional to the resistance of QGY-7703 cells to Taxol and doxorubicin, manipulation of Bcl-2 could be performed to enhance the sensitivity of liver cancer to chemotherapeutic agents.
...
PMID:Chemosensitivity of human hepatocellular carcinoma cell line QGY-7703 is related to bcl-2 protein levels. 1056 79

This study demonstrates that two anticancer drugs, taxol and doxorubicin (Dox), can kill human hepatoblastoma HepG2 cells in a dose-dependent manner via the induction of apoptosis. Characteristic events, including externalization of phosphatidylserine, cytoplasmic shrinkage, chromatin condensation and DNA degradation, were observed in a large majority of the drug-treated cells. DNA fragmentation showed that a ladder of DNA fragments of approximately 200 bp multiples was observed in taxol-treated, but not in Dox-treated, cells. In addition, the expression patterns of Bcl-2 family members during taxol or Dox treatment were investigated. Results from Western blot analysis indicated that HepG2 cells did not express either the death repressor Bcl-2, or the death promoters Bcl-XS and Bax. However, during the apoptotic process one death repressor, Bcl-XL, and two death promoters, Bak and Bad, were expressed. The expression levels of Bcl-XL and Bak remained unchanged, whereas the level of Bad was down-regulated. As the ratio between death repressors and death promoters in the Bcl-2 family will determine the sensitivity of cells to apoptotic stimuli, the findings suggest that the changed expression patterns of Bcl-2 family proteins caused by anticancer drugs in liver cancer cells may be involved in chemoresistance.
...
PMID:Expression of Bcl-2 family proteins during chemotherapeutic agents-induced apoptosis in the hepatoblastoma HepG2 cell line. 1069 52

c-Myc has been documented to be both a positive and a negative signal for the induction of apoptosis. It is well known that overexpression of the c-myc gene induces apoptosis of normal cells, but the result of a reduction in its expression is not fully understood. We examined whether a reduction in c-myc expression would induce apoptosis in human liver cancer cells. Specifically, antisense and sense oligodeoxynucleotides (oligos) against the human c-myc mRNA were synthesized, mixed with a liposome reagent at various ratios, and were applied to the liver cancer-derived cell lines, HCC-T, HepG2, and PLC/PRF/5. To exclude effects resulting from using oligos, plasmid vectors expressing the full-length c-myc cDNA in both sense and antisense orientations under the control of the Cre/loxP system were generated. Monoclonal cell lines including these plasmid vectors were produced and Cre was supplied by adenovirus infection. Apoptosis was determined morphologically and c-Myc and Bcl-2 expression was examined by Western blotting. The antisense myc significantly inhibited the proliferation of the cells within two days, while neither the liposome reagent alone nor sense myc did so. Most of the cells were rounded up by the antisense-treatment and nuclear fragmentation and DNA ladder formation were detected after two days in antisense c-myc-treated cells. Antisense c-myc largely reduced c-Myc and partially Bcl-2 expression; overexpression of Bcl-2 partially rescued from apoptosis in HCC-T and HepG2 cells. These results suggest that the massive reduction in c-myc mRNA induces apoptosis in liver cancer cell lines and consequent decrease in Bcl-2 enhances the cell death. c-Myc reduction under the Cre/loxP switching system may be a useful tool for the clarification of c-myc-related cellular mechanisms in differentiation and proliferation.
...
PMID:Reduction of c-myc expression by an antisense approach under Cre/loxP switching induces apoptosis in human liver cancer cells. 1138 22

In prostate carcinoma, overexpression of the anti-apoptotic gene Bcl-2 has been found to be associated with resistance to therapies including radiation and androgen ablation. Restoring the balance of Bcl-2 family members may result in the induction of apoptosis in prostate cancer cells previously resistant to treatment. To accomplish this, a strategy involving overexpression of the pro-apoptotic gene Bax was executed. The use of cytotoxic genes such as Bax require selective expression of the gene. In this study, we examined the ability of selective expression of Bax protein directed by a prostate-specific promoter to induce apoptosis in human prostate carcinoma. A second-generation adenoviral vector was constructed with the modified prostate-specific probasin promoter, ARR2PB, directing expression of an HA-tagged Bax gene and a green fluorescent protein reporter translated from an internal ribosome entry site (ARR2PB.Bax.GFP). ARR2PB promoter activity is tightly regulated and highly prostate specific and is responsive to androgens and glucocorticoids. The prostate-specific promoter-Bax-GFP transgene cassette was inserted into a cloning site near the right inverted terminal repeat of the adenoviral vector to retain specificity of the promoter. LNCaP cells infected with Ad/ARR(2)PB.Bax.GFP showed high levels of Bax expression 48 h after infection resulting in an 85% reduction in cell viability. Importantly, LNCaP cells stably transfected to overexpress Bcl-2 showed similar patterns of cell death when infected with Ad/ARR(2)PB.Bax.GFP, an 82% reduction in cell viability seen 48 h after infection. Apoptosis was confirmed by measuring caspase activation and using the TUNEL assay. Tissue specificity was evaluated using A549 cells (lung adenocarcinoma), SK-Hep-1 (liver cancer) cells, and Hela (cervical cancer) cells which did not show detectable expression of virally delivered Bax protein or any increase in cell death. Systemic administration of Ad/ARR2PB. Bax.GFP in nude mice revealed no toxicity in liver, lung, kidney, or spleen. This study shows that infection with the second-generation adenovirus, ARR2PB.Bax.GFP, results in highly specific cytotoxicity in LNCaP cells, and that consequent overexpression of Bax in prostate carcinoma, even in the context of high levels of Bcl-2 protein, resulted in apoptosis. These results suggest that a second-generation adenovirus-mediated, prostate-specific Bax gene therapy is a promising approach for the treatment of prostate cancer.
...
PMID:Prostate-specific expression of Bax delivered by an adenoviral vector induces apoptosis in LNCaP prostate cancer cells. 1157 75

It is known that proliferation and apoptosis are closely related phenomena in liver cancer cells. In this study, using surgical specimens from 42 patients with hepatocellular carcinoma (HCC), we investigated the expression and localization of Bcl-xL, an antiapoptosis-related protein of the Bcl-2 family. Using Western blotting, Bcl-xL expression was detected in both cancerous and non-cancerous specimens from all of the HCC patients, and elevated Bcl-xL levels were found in cancerous specimens from two thirds of the patients. In normal human liver specimens, Bcl-xL was found mainly in the cytoplasm of hepatocytes, although it was also found in the cytoplasm of bile duct cells in Glisson's capsule by immunohistochemical staining. To the best of our knowledge, this is the first report of Bcl-xL overexpression and localization in HCC specimens. Bcl-xL was found not only in the cytoplasm of HCC cells, but also in the nuclei of some HCC cells, suggesting that Bcl-xL is involved in the progression of HCC cells in vivo.
...
PMID:Bcl-xL overexpression in human hepatocellular carcinoma. 1216 94

Farnesyltransferase inhibitors (FTIs) block the growth of tumor cells in vitro and in vivo with minimal toxicity toward normal cells. In general, inhibition of protein farnesylation results in G0/G1 cell cycle block, G2/M cell cycle arrest, or has no effect on cell cycle progression. One aspect of FTI biology that is poorly understood is the ability of these drugs to induce cancer cell growth arrest at the G2/M phase of cell cycle. In the present study, we investigated the effects of the farnesyltransferase inhibitor FTI-277 on two human liver cancer cell lines, HepG2 and Huh7. Treatment of these cells with FTI-277 inhibited Ras farnesylation in a dose-dependent manner. Both HepG2 and Huh7 cell growth was inhibited by FTI-277 and cells accumulated at the G2/M phase of the cell cycle. In HepG2 and Huh7 cells, FTI-277 induced an up-regulation of the cyclin-dependent kinase inhibitor p27(Kip1) without affecting the cellular levels of p53 and p21(Waf1). This event correlated with reduced activity of the cyclin-dependent kinase 2 and cyclin-dependent kinase 1. Moreover, increased expression of Bcl-2 protein was observed in HepG2 and Huh7 cells treated with FTI-277, and this was coincidental with reduced association between Raf-1 and Bcl-2. Finally, transient transfection of a dominant-negative Ras allele induced Bcl-2 expression and reduced Bcl-2/Raf-1 association demonstrating a requirement for Ras. Taken together, these findings show that increased expression of p27(Kip1) and Bcl-2 is concomitant with altered association between Ras, Raf-1 and Bcl-2 and suggest that this is responsible for the growth-inhibitory properties of FTI-277.
...
PMID:Growth inhibition by the farnesyltransferase inhibitor FTI-277 involves Bcl-2 expression and defective association with Raf-1 in liver cancer cell lines. 1248 48

3-Bromopropionylamino benzoylurea (JIMB01) is a small molecular weight compound (MW 313) that has been synthesized in our laboratory. This compound showed antiproliferative activities in a panel of thirteen human tumor cell lines with IC(50) values in the range of 0.25 to 0.51 micro M for leukemia and lymphoma cell lines and 0.33 to 9.26 micro M for solid tumor cell lines. The primary action of JIMB01 is to inhibit microtubule polymerization but not depolymerization. A 4 micro M concentration of the compound caused a complete inhibition of microtubule assembly in a cell-free reaction. An increase in the number of human hepatocarcinoma cells blocked in the M-phase was detected 12hr after exposure to JIMB01. The kinase activity of cyclin B1, which is responsible for the G(2)/M transition, was increased accordingly. Bcl-2 phosphorylation became visible, in a western blot, within 6hr in hepatocarcinoma cells treated with JIMB01 at 0.8 micro M or higher. JIMB01-induced apoptosis in liver cancer cells was confirmed by morphological methods, flow cytometry, as well as DNA gel electrophoresis, which clearly demonstrated DNA degradation in the form of a multiple-unit DNA ladder. Furthermore, in vivo experiments using nude mice showed that intraperitoneal injection of JIMB01 at 15mg/kg (with seven injections at 4-day intervals) significantly inhibited the growth of a human hepatocarcinoma (BEL-7402) by 66% in tumor volume (P=0.01), at least compatible to the inhibition by vincristine (43% inhibition), indicating good bioavailability of the compound in the circulation. Side-effects of the compound were not observed, and the body weight of the treated mice remained stable during the 4-week treatment. Since JIMB01 is a small compound, targets a specific molecule in tumor cells, and has promising activity against human hepatocarcinoma in vivo, we believe JIMB01 merits consideration for further investigation.
...
PMID:Inhibition of microtubule polymerization by 3-bromopropionylamino benzoylurea (JIMB01), a new cancericidal tubulin ligand. 1275 5

Exposure to agonists of peroxisome proliferator-activated receptor alpha (PPARalpha) causes liver cancer in rodents, with aged animals being more susceptible than their younger counterparts to this effect. Treatment with these chemicals produced a five- to sevenfold higher yield of grossly visible hepatic tumors in old rats compared to young animals. The enhanced susceptibility of the aged livers to the carcinogenic effect of PPAR agonists could not be explained by differences in levels of peroxisomal and/or cell proliferation between young and old animals, as neither of these responses was exaggerated with aging. Reported studies have shown that activating PPARalpha results in the suppression of hepatic apoptosis. This effect is expected to diminish the ability of the liver to purge itself of pre-existing neoplastic cells, allowing them to progress to tumors. New findings from our laboratories show that the aged liver is exceedingly sensitive to the antiapoptotic effect of PPAR agonists. In addition, aged livers showed remarkably higher levels of the antiapoptotic protein Bcl-2 than livers of young, adult, and middle-aged animals. Interestingly, the PPARalpha agonist Wy-14,643 significantly diminished elements of the proapoptotic machinery (e.g., Bax, caspases, and fas) in the aged liver, while remarkably increasing elements of this machinery in younger animals. Taken together, while activation of PPARs appears to inhibit apoptosis in livers of senescent animals, activating these receptors seems to stimulate the apoptotic machinery in young animals. This paradoxical effect may be responsible for the exaggerated sensitivity of the aged liver to the carcinogenic effect of agents that activate PPARs.
...
PMID:Enhanced hepatocarcinogenicity due to agonists of peroxisome proliferator-activated receptors in senescent rats: role of peroxisome proliferation, cell proliferation, and apoptosis. 1280 35

The present study was to investigate the chemopreventive effects of tea pigments. In vitro study showed that tea pigments induced QR activity and GST activity in Hep G2 cells. Three animal models were used to observe the preventive effects of tea pigments on liver cancer, colorectal cancer and oral cancer. Oral administration of 0.1% tea pigments increased GST activity in rat liver by 18%, and this increase was accompanied by the significant increase of GST 1-1, 1-2, and 3-3 protein expression in rat liver. Tea pigments inhibited the proliferating cell nuclear antigen labeling index (PCNA-LI), the expression of Bcl-2 protein and ras-p21 protein, and induced the expression of Bax protein in rat colorectal cancer. PCNA-LI, silver-stained nucleolar organizer regions (AgNOR) and epidermal growth factor receptor (EGFR) expression were also inhibited by tea pigments in hamster oral cancer. Our results suggested that tea pigments had chemopreventive effects on cancer, and the anti-cancer properties may be due to the activation of detoxifying enzymes such as QR and GST, the inhibition of cell proliferation and the induction of apoptosis.
...
PMID:[Studies on cancer chemoprevention by tea pigments]. 1496 10

1 2 3 4 5 6 7 8 9 10 Next >>