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)

Isocostunolide is a sesquiterpene lactone isolated from the roots of Inula helenium. Its chemical structure was determined by NMR and FAB-MS spectra. No biological activities of this compound have yet been reported. In this study, we found isocostunolide could effectively induce cytotoxicity in three cancer cell lines (A2058, HT-29, and HepG2), with an IC(50) of 3.2, 5.0, and 2.0 micro g/mL, respectively. DNA flow cytometric analysis indicated that isocostunolide actively induced apoptosis of cancer cells accompanied by a marked loss of G0/G1 phase cells. To address the mechanism of the apoptotic effect of isocostunolide, we analyzed the induction of apoptosis-related proteins in A2058. The levels of pro-caspase-8, Bid, pro-caspase-3, and poly(ADP-ribose) polymerase (PARP) decreased. However, the level of Fas was increased markedly in a dose-dependent manner. Furthermore, this compound markedly induced a depolarization of mitochondrial membranes to facilitate cytochrome c release into cytosol. The findings suggest that isocostunolide may activate a mitochondria-mediated apoptosis pathway. To address this, we found that isocostunolide-induced loss of mitochondrial membrane potential occurred via modulation of the Bcl-2 family proteins. The production of intracellular reactive oxygen species (ROS) in A2058 was not elicited. In summary, for the first time, we have isolated and characterized isocostunolide from I. helenium. This compound induces apoptosis through a mitochondria-dependent pathway in A2058 cells.
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PMID:Isocostunolide, a sesquiterpene lactone, induces mitochondrial membrane depolarization and caspase-dependent apoptosis in human melanoma cells. 1669 6

Twenty-five children (19 M:6 F) with newly diagnosed ALL with median age of 5.5 years (1 month-12 years) were enrolled in the study. Apoptosis regulator proteins bcl-2 and bax were measured in all patients using alkaline phosphatase anti-alkaline phosphatase method. Twenty-one patients were positive for bcl-2 and 23 cases for Bax, although expression levels varied. Patients who presented with splenomegaly or hepatomegaly < 5 cm expressed significantly higher levels of bcl-2 and bax protein expression. Neither of age ( < or >10 years), sex, generalized lymphadenopathy, WBC ( < or >50,000/mul) or FAB subtype was associated with high levels of bcl-2 or bax protein expression. Patients with higher mean hemoglobin levels (p = 0.009), high blast % in bone marrow (p = 0.02), immature immunophenotype (p = 0.001) exhibited signifxicantly higher bcl-2 levels. Bcl-2/bax ratio correlated inversely with TLC at presentation (p = 0.022; r = - 0.456) and in B-lineage leukemic cells as compared to T-lineage cells (p = 0.002). Bcl-2/bax ratio did not correlate with any other variable measured. Bcl-2 and bax protein co-express in ALL and high bcl-2/bax ratio correlates with good prognosis features.
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PMID:Expression of apoptosis regulators Bcl-2 and Bax in childhood acute lymphoblastic leukemia. 1736 91

Bioassay directed fractionation and purification led to the successful isolation of a furano sesquiterpene, Methyl 5-[(1E,5E)-2,6-Dimethyl octa-1,5,7-trienyl] furan-3-carboxylate (MDTFC), a bioactive component from a soft coral, Sinularia kavarittiensis. Its structure was determined by analyzing (1)H, (13)C NMR and FAB-MS. The results show that MDTFC could efficiently and selectively inhibit the proliferation of several human cancer cell lines. Among all the cell lines, THP-1 was found to be most sensitive (IC(50) 29.59 microM), whereas the peripheral blood mononuclear cells were least effected (IC(50) 464.16 microM). The molecular mechanism of MDTFC mediated apoptosis was investigated for the first time. Induction of apoptosis in THP-1 cells was characterized by cell membrane blebbing, chromatin condensation, DNA fragmentation, and decrease in level of pro-caspases 3, 9 and increase in Bax/Bcl-2 ratio. Our results were further strengthened through cleavage of poly (ADP-ribose) polymerase, reduction of mitochondrial membrane potential (Psim) and cytosolic release of cytochrome c, which are key events during apoptosis. Moreover, phosphatidyl serine exposure and appearance of sub-G1 peak also demonstrated cell death, when analyzed by flow cytometry. DNA fragmentation was prevented moderately when pretreated with caspase-9 inhibitor (Z-LEHD-FMK) and largely with caspase-3 inhibitor (Z-DEVD-FMK). In summary, MDTFC mediated apoptosis involves mitochondria-dependent pathway and the present compound of marine origin might have a therapeutic value against human cancer cell lines and especially on leukemia cells.
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PMID:Furano-sesquiterpene from soft coral, Sinularia kavarittiensis: induces apoptosis via the mitochondrial-mediated caspase-dependent pathway in THP-1, leukemia cell line. 1928 88

Transformation of leukemic cells is associated with delay in maturation and in apoptosis, and to altered responsiveness to growth factors. However, some studies have revealed that Fas (CD95/APO1) which mediates apoptotic signal and decrease of anti-apoptotic Bcl-2 are frequently observed in acute myeloid leukemia (AML) M4/M5 leukemic cells. The aim of the study was to compare cytomorphology and cytochemistry of bone marrow (BM) apoptotic leukemic cells to preserved peripheral blood (PB) leukemic cells in our patient, a 76-year-old man with AML-M5b treated at Zagreb University Hospital Center. BM and PB of the AL patient were analyzed after Pappenheim and cytochemical stainings, and leukemic cells were classified according to FAB and WHO classification. Analysis of PB revealed leukocytosis and 80-90% monocytic cells (46% monoblasts, 29% promonocytes and 11% monocytes). Only a few preserved monoblasts and promonocytes were found in BM, together with numerous morphologically altered cells with characteristic chromatin condensation and pyknosis of nucleus, as well as nuclear fragmentation and formation of apoptotic bodies. Thus, cytomorphology of PB leukemic cells pointed to proliferation of immature monocytic cells, and cytomorphology of BM to cell apoptosis. Cytochemistry of PB monocytic cells and BM apoptotic cells confirmed monocytic cell lineage because esterase was strongly positive in almost all BM apoptotic leukemic cells and PB leukemic cells, and esterase was completely inhibited with sodium fluoride. On the basis of these findings, AML-M5b was diagnosed in our patient. There are many possible explanations for our observation of BM leukemic cell apoptosis in a patient with AML-M5. The most reliable one is that apoptosis was induced ex vivo after BM aspiration in course of the air drying of BM specimen before staining. Mass BM leukemic cell apoptosis that was recorded in contrast to numerous preserved leukemic cells in PK could be probably connected to unfavorable ratio of relatively low concentration of cytokines in relation to high leukemic cell number in BM aspirated cytologic specimen.
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PMID:Apoptosis of leukemic cells: a case report. 2069 59

Age-related macular degeneration (AMD) is the leading cause of vision loss and blindness among the elderly. Although the pathogenesis of this disease remains still obscure, several researchers have report that death of retinal pigmented epithelium (RPE) caused by excessive accumulation of A2E is crucial determinants of AMD. In this study, the preventive effect of Vaccinium uliginosum L. (V.U) extract and its fractions on AMD was investigated in blue light-irradiated human RPE cell (ARPE-19 cells). Blue light-induced RPE cell death was significantly inhibited by the treatment of V.U extract or its fraction. To identify the mechanism, FAB-MS analysis revealed that V.U inhibits the photooxidation of N-retinyl-N-retinylidene ethanolamine (A2E) induced by blue light in cell free system. Moreover, monitoring by quantitative HPLC also revealed that V.U extract and its fractions reduced intracellular accumulation of A2E, suggesting that V.U extract and its fractions inhibit not only blue light-induced photooxidation, but also intracellular accumulation of A2E, resulting in RPE cell survival after blue light exposure. A2E-laden cell exposed to blue light induced apoptosis by increasing the cleaved form of caspase-3, Bax/Bcl-2. Additionally, V.U inhibited by the treatment of V.U extract or quercetin-3-O-arabinofuranoside. These results suggest that V.U extract and its fractions have preventive effect on blue light-induced damage in RPE cells and AMD.
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PMID:Preventive effect of Vaccinium uliginosum L. extract and its fractions on age-related macular degeneration and its action mechanisms. 2658 89


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