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)

Environmentally exposed erionite is a potent and unique inducer of malignant pleural mesothelioma (MPM) in Central Anatolia in Turkey. Previous studies have shown that erionite induced MPM has different biological behavior than asbestos induced MPM. Although impaired apoptosis has been implicated in tumor biology, the relationship between the type of environmental exposure and apoptosis has not yet been evaluated in MPM. The purpose of this study was to determine the expression of apoptosis regulating proteins and their prognostic significance in erionite and asbestos induced MPM. Thirty-five patients with MPM (16 erionite and 19 asbestos induced), and 17 patients with adenocarcinoma were comparatively evaluated. Expression of Bcl-2, Bax, Fas and Fas Ligand, were assessed by immunohistochemistry. Bcl-2 and Fas did not stain in almost all specimens. The staining extension of Bax was 13.75 +/- 19.27%, 5.89 +/- 14.51% and 7.38 +/- 14.53% for erionite and asbestos induced MPM and adenocarcinoma, respectively (p = 0.566). The staining extension of Fas Ligand was 26.87 +/- 31.87%, 46.10 +/- 37.30% and 26.47 +/- 23.23% for erionite and asbestos induced MPM, and adenocarcinoma, respectively (p = 0.123). Bax negative patients in erionite group had longer survival than Bax positive patients (18 months versus 14 months) (p = 0.06). Fas Ligand positive patients showed statistically better survival than Fas Ligand negative patients in all MPM group (15 months versus 12 months) (p = 0.05). Although all proteins expressed in similar extension in all samples, Bax staining displayed an inverse relation with survival in erionite group. This may implicate a difference in Bax functioning in erionite induced MPM. However, Fas Ligand may be functionally intact to reduce tumor survival.
Lung Cancer 2005 Nov
PMID:Prognostic significance of Bax and Fas ligand in erionite and asbestos induced Turkish malignant pleural mesothelioma. 1604 60

Lung cancer has emerged as one of the leading causes of cancer death in most developed and many developing countries of the world. In the absence of effective screening and early detection methods of lung cancer and overall poor prognosis, the 5-year survival following treatment has not improved significantly over the last two decades. It is hoped that the risk of the disease can be minimized by preventive measures. One aspect of lung cancer prevention emphasizes the cessation of tobacco smoking, and another strategy envisages reversal or restriction of the process of lung carcinogenesis by chemopreventive intervention. The latter strategy, however, demands a deeper understanding of the pathogenesis of the disease and the identification of the ideal point of intervention. In the present investigation, we assessed the role of the antioxidant tea components theaflavins (TF) and epigallocatechin gallate (EGCG) for their chemopreventive potential and molecular mechanism of action when administered at the post-initiation phase of lung carcinogenesis in an experimental mouse model. We serially examined the histopathological changes in the lung of mice administered benzo(a)pyrene and correlated them with the frequency of proliferative and apoptotic cells in situ as well as with the expression of H-ras, c-Myc, p53, and Bcl-2 genes, which play key roles in the histopathogenesis of neoplasia. Our findings indicate that both TF and EGCG can influence gene expression to modulate the process of carcinogenesis through the regulation of apoptosis. This results in a lowered incidence and delayed onset of preinvasive lung lesions.
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PMID:Black tea extract can modulate protein expression of H-ras, c-Myc, p53, and Bcl-2 genes during pulmonary hyperplasia, dysplasia, and carcinoma in situ. 1605 Aug 5

Peroxisome proliferator-activated receptor-gamma (PPAR-gamma) is a member of the nuclear hormone receptor superfamily of ligand-activated transcription factors and a crucial regulator of cellular differentiation. PPAR-gamma ligands have been demonstrated to inhibit growth of several cancer cells. In this study, two human lung cancer cells (NCI-H23 and CRL-2066) and one human lung normal cell (CRL-202) were used for the experiments. The results showed that in consistence with the loss of viability, troglitazone (TGZ) induced apoptosis of CRL-2066 and NCI-H23 cells but not CCL-202 cells. TGZ upregulated PPAR-gamma expression in all the three lung cell lines, especially in the cancer cells. In association of the time-dependent inhibition of the cell proliferation, TGZ downregulated the expression of Bcl-w and Bcl-2 but activated extracellular signal-regulated kinase (ERK)1/2 and p38, suggesting that the growth-inhibitory effect of TGZ is associated with the reduction of Bcl-w and Bcl-2 and the increase of ERK1/2 and p38 activation. SAPK/JNK activation assay showed a decreased activity in all the three cell lines tested after TGZ treatment. It was also demonstrated that TGZ could activate PPAR-gamma transcriptionally. We conclude that TGZ inhibits growth of human lung cancer cells via the induction of apoptosis and the inhibition of cell growth, at least in part, in a PPAR-gamma-relevant manner. The mechanism of TGZ is associated with the activation of ERK and p38, the reduction of SAPK/JNK activity, and the alteration of Bcl-w and Bcl-2.
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PMID:Activation of peroxisome proliferator-activated receptor-gamma by troglitazone (TGZ) inhibits human lung cell growth. 1614 72

The fragile histidine triad (FHIT) gene is a frequent target of deletions in lung cancer. Previous studies have shown that FHIT gene transfer into lung cancer cells lacking FHIT expression results in induction of apoptosis. However, the effect of FHIT expression on apoptosis induced by chemotherapeutic agents and its intracellular mechanism is poorly understood. This study was undertaken to elucidate the effect of FHIT expression and the role of Bcl-2-caspase signaling in paclitaxel-induced apoptosis in lung cancer cells. NCI-H358 lung cancer cells, which lack FHIT expression, were stably transfected with plasmid vector containing FLAG-tagged wildtype FHIT. We investigated effects of paclitaxel on apoptosis, activation of caspase system and expression of Bcl-2 family. We next evaluated whether these effects were reversed by blocking FHIT expression using siRNA. Paclitaxel enhanced apoptosis in FHIT-expressing cells compared to that in control vector-transfected cells, and this enhancement was suppressed by siRNA treatment. Activities of caspase-3 and caspase-7, but not of caspase-8, were higher in FHIT-expressing cells than in control vector-transfected cells, and this was reduced by siRNA treatment. When caspase activation was blocked by a pan-caspase inhibitor in FHIT-expressing cells, paclitaxel-induced apoptotic cell death was decreased similar to that in control vector-transfected cells. Bcl-2 and Bcl-xL expressions were down-regulated after paclitaxel treatment in FHIT-expressing cells, whereas Bax and Bad expressions were up-regulated. These were reversed by siRNA treatment. These results indicate that paclitaxel-induced apoptosis enhanced by FHIT expression in lung cancer cells might be associated with modulation of Bcl-2-caspase signaling.
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PMID:FHIT protein enhances paclitaxel-induced apoptosis in lung cancer cells. 1623 22

Lung cancer is a complex group of diseases but each lesion is thought to originate from a single mutated progenitor cell. It is evident that multiple genetic changes are involved in the generation of each specific type of lung cancer. Due to the high complexity of these processes and rapid metastasis, treatment of advanced lung cancer, particularly of NSCLCs, is far from satisfactory. Thus, there is a need for innovative strategies for modulation of adverse alteration in protooncogene or tumor suppressor genes so that lung carcinogenesis can be suppressed or delayed. To this end, we have evaluated the effects of tea compounds (theaflavins, epicatechin-gallate and epigallo-catechin-gallate) on proliferation and apoptosis and associated gene expression in a highly metastatic human lung cancer cell line NCI-H460. Significant reduction of cell proliferation, detected in situ by BrdU incorporation, and induction of apoptosis, assessed by the by the TUNEL method, were noted following treatments. Expression of p53, Bcl-2, c-Myc and H-Ras, was localized by immunocytochemistry and analysed by Western blotting. Tea compounds upregulated expression of p53, downregulated expression of Bcl-2 but there was no significant influence on H-ras and c-Myc expressions. It is suggested that tea compounds can influence genetic alteration to disfavour, growth and survival of lung cancer cells.
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PMID:Inhibition of growth, induction of apoptosis and alteration of gene expression by tea polyphenols in the highly metastatic human lung cancer cell line NCI-H460. 1623 94

Small-cell lung cancer (SCLC) is a tobacco-related malignancy that usually presents in an extensive and therefore incurable stage. Although initially sensitive to platinum agent-based therapy, SCLC rapidly becomes refractory to chemotherapy, leading to disease recurrence and ultimately patient death. Treatment options following failure of first-line platinum agent-based therapy are limited. Small-cell lung cancer is characterized by molecular aberrancies such as overexpression of the antiapoptotic protein Bcl-2, which is regulated in part by the inhibitory IkappaB, a target of the ubiquitin-proteasome degradative pathway. Bortezomib is a proteasome inhibitor that can decrease Bcl-2 expression through diminished IkappaB degradation. Efforts to promote apoptosis in SCLC through the integration of bortezomib into therapy are under way.
Clin Lung Cancer 2005 Oct
PMID:Proteasome inhibition in small-cell lung cancer: preclinical rationale and clinical applications. 1625 Sep 31

Lung cancer is the leading cause of cancer death in many developed countries, including Taiwan. Quercetin, a widely distributed bioflavonoid, is well known to induce growth inhibition in a variety of human cancer cells. Quercetin glucuronides are the main circulating metabolites after dietary supplements with quercetin in humans. However, there is little information available as to how quercetin glucuronides affect human cancer cells. We investigated the effects of quercetin glucuronides in a human lung cancer cell line NCI-H209. We checked the cell viability, cell cycle checkpoint proteins, pro- and antiapoptotic proteins, caspase-3 activity, and gene expression by flow cytometry and Western blot. The viability of cells decreased in a dose- and time-dependent manner. Cell cycle analysis revealed a significant increase of the proportion of cells in G2/M phase and subG0/G1 phase (corresponding to apoptotic cells). Moreover, quercetin glucuronides increased the expressions of cyclin B, Cdc25c-ser-216-p, and Wee1 proteins, indicating the G2/M arrest. We also demonstrated a concurrent decrease of the mitochondrial membrane potential, release of cytochrome c, up-regulation of Bax, down-regulation of Bcl-2, and activation of caspase-3, and subsequently, cleavage of poly(ADP-ribose) polymerase. In addition, quercetin glucuronide-induced apoptosis was totally blocked by the broad-spectrum caspase inhibitor benzyloxycarbonyl-Val-Ala-Asp fluoromethylketone. Taken together, we demonstrated that quercetin glucuronides inhibited proliferation through G2/M arrest of the cell cycle and induced apoptosis via caspase-3 cascade in the human lung cancer cell line NCI-H209. Delineation of the biological effects of specific major quercetin metabolites on chemotherapeutic potential or chemoprevention of human cancers warrants further investigation.
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PMID:Inhibition of lung cancer cell growth by quercetin glucuronides via G2/M arrest and induction of apoptosis. 1628 Apr 56

The aim of our study was to estimate the expression of the Bcl-xL gene, a member of Bcl-2 family, in NSCLC patients. A total of 60 consecutive patients diagnosed with NSCLC that underwent chemotherapy prior to surgery were reviewed. Bcl-xL expression was assessed on paraffin sections by in situ hybridization (ISH) and immunohistochemistry (IMH). We observed the presence of mRNA of Bcl-xL gene and its protein product overexpression in most patients (60 and 81.7%, respectively). In material examined no significant correlation was observed between the pattern of Bcl-xL or protein expression and any clinicopathological factors evaluated. The expression of Bcl-xL protein was low (less than 10% positive cells) in 11 patients (median survival time 29 months) as compared to 49 patients with overexpression (median survival time 21.0 months). The difference was not of statistic significance (p=0.27). In examined group the Bcl-xL mRNA was found in 36 patients, while it was absent in 24 cases. Median survival time was 14.5 and 86.5 months, respectively (p=0.001). In addition, 19.4% of 5-year survivals were achieved in patients with overexpression and 54.2% in patients with no mRNA present (p=0.002). The percentage of 5-year survival in patients with protein expression assessed by IMH was 30.6% (p=0.31). The estimation of Bcl-xL expression on mRNA and protein level was compared by the means of sign test and the significant difference was found (p=0.009). The inconsistency was related to 35% of cases. In comparison with IMH, ISH technique appeared to be more specific and accurate in assessment of 5-year survival (25 and 65%; 65 and 70%, respectively). The results of our study indicate that Bcl-xL mRNA overexpression may suggest poor prognosis in NSCLC.
Lung Cancer 2006 Jan
PMID:Estimation of prognostic value of Bcl-xL gene expression in non-small cell lung cancer. 1629 99

Lung cancer is the leading cause of cancer-related deaths throughout the world. Extracts of medicinal plants are believed to contain different chemopreventive or chemotherapeutic compounds. In this study, we determined the anti-cancer property of one of the traditional Indian medicine Rasagenthi Lehyam (RL) for the treatment of lung cancer. Two lung cancer cell lines (A-549 and H-460) and one normal bronchial epithelial (BEAS-2B) cell line were used to test the chemotherapeutic effect of RL. Out of five fractions of RL, chloroform fraction of RL (cRL) demonstrated a significant inhibition of cell proliferation and induction of apoptosis in A-549 and H-460 cells but not in normal BEAS-2B cells. The cRL fraction up-regulated the pro-apoptotic genes p53 and Bax and induced caspase-3 activation, and down-regulated the pro-survival gene Bcl-2 in both the lung cancer cell lines. Also, nuclear export of p53 was seen in cRL-treated lung cancer cells. In addition, cRL induced G2/M arrest of cell cycle and enhanced the radio-sensitivity of both the lung cancer cell lines. This study suggests that cRL may prove to be a potent anti-cancer agent that may be used for the treatment of lung cancer. However, further studies are required to bring cRL into the mainstream of medicine in the treatment of lung cancer.
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PMID:A herbal medicine for the treatment of lung cancer. 1631 13

Ponicidin, an ent-kaurane diterpenoid derived from a constituent of the herbal supplement PC-SPES, Rabdosia rubescens, is recently reported to have anti-tumor effects on a large variety of cancers. In this study, we demonstrate that ponicidin exhibits cytotoxicity, induces apoptosis, disrupts the mitochondrial membrane potential, and triggers the activation of caspase-3, -8 and -9 in lung cancer A549 and GLC-82 cells. Ponicidin treatment of lung cancer cells caused downregulation of anti-apoptotic protein Bcl-2 and survivin as well as upregulaton of pro-apoptotic protein Bax in a time dependent manner when apoptosis ocurred. Ponicidin induced activation of caspase-3 can be blocked by a caspase-3-specific inhibitor z-DEVD-FMK Furthermore, the caspase-8-specific inhibitor z-IETD-FMK could block the ponicidin-induced activation of caspase-3, PARP cleavage, and prevented the release of cytochrome c from mitochondria into the cytoplasm. This indicate that activated caspase-8 initiates the release of cytochrome c during ponicidin-induced apoptosis. We therefore conclude that ponicidin has significant apoptosis-inducing effects by activation of caspase-3 -8, and -9 as well as downregulation of anti-apoptotic protein Bcl-2, survivin and upregulation of pro-apoptotic protein Bax, with caspase-8 acting as an upstream activator. The data offer a potential mechanism for ponicidin-induced apoptosis in lung cancer cells, suggesting that ponicidin may severve as an effective reagent for the treatment of lung cancer, and that in vivo anti-cancer effects as well as its potential clinical effectiveness need further investigation.
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PMID:Ponicidin, an ent-kaurane diterpenoid derived from a constituent of the herbal supplement PC-SPES, Rabdosia rubescens, induces apoptosis by activation of caspase-3 and mitochondrial events in lung cancer cells in vitro. 1653 82


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