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 aim of this study was to develop novel and less toxic therapy for human head and neck squamous cell carcinoma (HNSCCs) and to investigate the mechanism of quercetin-induced apoptosis in human laryngeal HeP2 cells and its effect on cisplatin induced apoptosis. Priming the cells with quercetin (40 microM) increased the apoptosis induced by cisplatin alone from 18.7% to 42.2% in HeP2 cells. Quercetin induced apoptosis via inhibition of Akt/PKB phosphorylation, an upstream kinase of pro-survival protein kinase cascade. Inhibition of Akt phosphorylation was coupled with a significant decrease of anti-apoptotic Bcl-2 and Bcl-XL. Quercetin caused a downregulation of Cu-Zn Superoxide Dismutase which perhaps led to an increase of reactive oxidative stress (ROS). The decrease of Bcl-2 and Bcl-XL along with this oxidative stress caused release of mitochondrial cytochrome c into the cytosol and subsequent induction of pro-caspase-9 processing. Inhibition of heat shock proteins may be another mechanism for the pro-apoptotic activity of quercetin. Cisplatin induced apoptosis appears to be partly due to induction of JNK activity which leads to the activation of endonucleases. Increased JNK activity led to increased phosphorylation of c-Fos. Cisplatin additionally appears to induce apoptosis by down-regulating the enzyme Nitric Oxide Synthase (NOS). Cisplatin also acts by increasing pro-apoptotic Bax concentration in the cells thereby leading to caspase-9 activation via the mitochondrial pathway. These results support the fact that quercetin and cisplatin act by separate pathways and demonstrate interactions between the pathways that result in synergistic actions. Possibly of greater potential value is the interaction of a conventional cytotoxic drug (cisplatin) and a nontoxic chemopreventive agent (quercetin) thereby allowing the use of less toxic doses of chemotherapy for treatment of HNSCCs.
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PMID:Molecular pathways in the chemosensitization of cisplatin by quercetin in human head and neck cancer. 1608 93

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

To investigate the effects of ATRA, acitretin and tazarotene on the growth and apoptosis of human tongue squamous cell carcinoma cell line Tca8113. The effect of retinoids on growth of Tca8113 cells in vitro was examined by MTT assay and Trypan blue exclusion assay. Cell cycle analysis, early apoptosis analysis with double staining with Annexin V-FITC and PI, and active caspase-3 analysis with the staining of FITC-conjugated monoclonal rabbit anti-active caspase-3 antibody were made by flow cytometer. Streptavidin-biotin complex (SABC) immunocytochemical assays were employed for the detections of Bax/Bcl-2 proteins expressions. Our results showed that the retinoids inhibited growth of Tca8113 cells in a dose- and time-dependent manner with maximal inhibition 24 h after treatment of 10(-5) mol/L. 10(-5) mol/L retinoids altered cell cycle distribution of Tca8113 cells, revealing an increase in G0/G1-phase population, a decrease in S-phase population and the inhibition of G1/S switching. 10(-5) mol/L retinoids significantly induced apoptosis of Tca8113 cells (all P < 0.05), elevated the cells population with detectable active caspase-3 (P < 0.05 for all), increased the number of cells forming Bax and decreased the number of cells forming Bcl-2 significantly (all P < 0.05). Acitretin played a most prominent role among the retinoids. It is concluded that the inhibition of cell cycle progress of Tca8113 cells by ATRA, acitretin and tazarotene is one of the possible mechanisms for proliferation arrest of Tca8113 cells elicited by the retinoids. The retinoids mediate apoptosis in Tca8113 cells that may be caspase-dependent through mitochondria pathway. High concentration retinoids inhibit growth of Tca8113 cells in vitro by interfering with proliferation and inducing apoptosis of cells. Acitretin may be an alternative medicine for the prevention and treatment of tongue squamous cell carcinoma.
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PMID:Effects of ATRA, acitretin and tazarotene on growth and apoptosis of Tca8113 cells. 1619 85

Chemokine C receptor 7 (CCR7) expression is important for lymphocyte homing to tissues. We hypothesized that CCR7 also plays a role in CD8(+) T-cell protection from apoptosis. Its expression was determined on circulating T cells in patients with cancer and related to that of molecules responsible for lymphocyte susceptibility/resistance to apoptosis. Peripheral blood mononuclear cells were obtained from 36 patients with squamous cell carcinoma of the head and neck and 16 normal controls. Multicolor flow cytometry was used to evaluate CCR7, Fas, Bax, and Bcl-2 expression in CD8(+) T cells. Annexin V binding to CD8(+)CCR7(+) and CD8(+)CCR7(-) T-cell subsets was compared. Fewer CD8(+)CCR7(+) T cells bound Annexin V than CD8(+)CCR7(-) T cells in normal control and patients (P < 0.0001). CCR7 expression correlated with higher Bcl-2 but lower Bax and Fas expression levels in CD8(+) T cells in both normal control and patients (P < 0.0001). In patients, the CD8(+)CCR7(+) subset was reduced relative to normal control (P = 0.008) and replaced with an excess of apoptosis-sensitive CD8(+)CCR7(-) T cells. To study CCR7 signaling, CD8(+) T cells were stimulated with CCR7 ligands, chemokine C ligands 19 or 21. Ligand binding to CCR7 resulted in phosphorylation of Akt and increased Bcl-2 expression in CD8(+)CCR7(+) T cells, suggesting that CCR7 protects effector T cells from apoptosis through the phosphatidylinositol 3-kinase/Akt pathway. The absence of CCR7 expression on the majority of CD8(+) T cells in the peripheral circulation of patients with squamous cell carcinoma of the head and neck contributes to apoptosis and a rapid turnover of these effector cells.
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PMID:Chemokine C receptor 7 expression and protection of circulating CD8+ T lymphocytes from apoptosis. 1627 74

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

4-Nitroquinoline 1-oxide (4NQO)-induced rat tongue carcinogenesis is a useful model for studying oral squamous cell carcinoma. The aim of this study was to investigate the expression of bcl-2 and bax during tongue carcinogenesis induced by 4NQO. Male Wistar rats were distributed into three groups of 10 animals each and treated with 50 ppm 4NQO solution through their drinking water for 4, 12 or 20 weeks. Ten animals were used as negative control. Although no histological changes were induced in the epithelium after 4 weeks of carcinogen exposure, bcl-2 and bax were over-expressed (P < 0.01) in all layers of the 'normal' epithelium. The expression levels were the same in all layers of epithelium for both the antibodies used (bcl-2 or bax). In dysplastic lesions at 12 weeks following carcinogen administration, the levels of bcl-2 and bax expression did not increase when compared to negative control with the immunoreactivity for bcl-2 being restricted to the superficial layer of epithelium. In well-differentiated squamous cell carcinoma induced after 20 weeks of treatment with 4NQO, bcl-2 was expressed in some cells of tumour islands. On the other hand, immunostaining for bax was widely observed at the tumour nests. The labelling index for bcl-2 and bax showed an increase (P < 0.05) after only 4 weeks of 4NQO administration. In conclusion, our results suggest that abnormalities in the apoptosis pathways are associated with the development of persistent clones of mutated-epithelial cells in the oral mucosa. Bcl-2 and bax expression appears to be associated with a risk factor in the progression of oral cancer.
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PMID:Abnormal expression of bcl-2 and bax in rat tongue mucosa during the development of squamous cell carcinoma induced by 4-nitroquinoline 1-oxide. 1630 43

The incidence and prevalence of premalignant and malignant skin lesions including squamous cell carcinoma (SCC) of the skin are increasing worldwide. The aim of the study was to determine TP53, Bcl-2 and growth hormone receptor (GHR) expression in SCC and to investigate relative importance of these proto-oncogenes in its biological behavior. Expression of TP53, Bcl-2 and GHR was determined by immunohistochemistry in 27 SCC specimens and adjacent perilesional skin. The relative proportion of immunoreactive cells was counted with semiquantitative method. TP53 positivity was detected in 24 (89%), Bcl-2 in 18 (67%) and GHR in 25 (93%) of 27 SCC specimens investigated. In comparison with perilesional skin, TP53 and GHR positivity was significantly increased, and Bcl-2 positivity significantly decreased in SCC. Increased TP53 expression in SCC lesions implies that Tp53 mutation is an early and crucial event in its development. Increased GHR expression suggests a role of growth hormone in the development of SCC.
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PMID:TP53, Bcl-2 and growth hormone receptor expression in cutaneous squamous cell carcinoma. 1635 91

Taxanes, a new class of antitumor drugs, are effective against a large number of human tumors, although there are problems with drug resistance. The novel taxane, IDN5109, is characterized by its high tolerability, antitumor efficacy, ability to overcome multidrug resistance, and oral bioavailabilty. We investigated the cellular response of IDN5109 to head and neck squamous cell carcinoma (HNSCC), and compared the antitumor activity of IDN5109 with that of paclitaxel. This is the first demonstration of antitumor effects of IDN5109 on HNSCC. In in vitro experiments, IDN5109 showed antiproliferative effects against HNSCC cell lines. After treatment with IDN5109, Bcl-2 and Bcl-XL were down-regulated, Bax was up-regulated, and caspase-3 was activated. After treatment with IDN5109, concentrations of both VEGF and IL-8 in the culture supernatant of HNSCC cells decreased. In in vivo experiments, the oral administration of IDN5109 showed antitumor effects against HNSCC tumor xenografts. Immunohistochemistry showed that IDN5109 inhibited tumor angiogenesis and induced apoptosis in HNSCC cells, producing a decreased blood vessel density and increased apoptosis index. On the basis of these results, IDN5109 is useful as a chemotherapeutic agent against HNSCC.
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PMID:Antitumor effects of IDN5109 on head and neck squamous cell carcinoma. 2678 Sep 76

Markers of cell proliferation (Ki-67 antigen) and apoptosis (Bax, Bcl-2) were studied in an experimental system of induced oral carcinogenesis in Syrian golden hamsters. Thirty-seven animals were divided into one control group and three experimental groups, which were treated with a carcinogen and sacrificed at 10, 14 and 19 weeks after treatment. The histological status of the lesions in the three experimental groups corresponded well with tumour advancement (from oral mucosal dysplasia to moderately differentiated squamous cell carcinoma). Tumour sections were studied using monoclonal antibodies against Bax, Bcl-2 and Ki-67 proteins. Pro-apoptotic Bax expression maintained high levels during all stages of oral carcinogenesis. Anti-apoptotic Bcl-2 expression decreased significantly in dysplastic and early invasion lesions and consequently increased almost to normal tissue level in consequent stages. Finally, Ki-67 expression increased sharply in initial stages of oral carcinogenesis, but significantly decreased in later stages.
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PMID:Cell proliferation and apoptosis culminate in early stages of oral oncogenesis. 1646 33


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