Gene/Protein Disease Symptom Drug Enzyme Compound
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Query: UMLS:C0023418 (leukemia)
 93,477 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

Cellular resistance to chemotherapeutic agents is attributable to several mechanisms, including alteration of topoisomerase IIa gene expression. Our previous studies have shown that transient transfection with a vector containing either Drosophila or human topoisomerase IIalpha gene into drug-resistant tumor cells enhanced their drug sensitivity. Furthermore, we constructed a recombinant adenovirus, Ad-hTopoIIalpha, containing the human topoisomerase IIa gene that was able to selectively increase etoposide sensitivity in drug-resistant tumor cells. We also examined Ad-hTopoIIalpha for therapeutic efficacy in vitro using additional etoposide-resistant cell lines, including a mouse breast cancer cell line and a human leukemia cell line. The etoposide-resistant mouse breast cancer cell line FvP, which is derived from FM3A, and etoposide-resistant human breast cancer cell line, MDA-VP, which derived from MDA-P cells showed increased sensitivity to etoposide as well as increased expression of human Topoisomerase IIa mRNA, but this was not seen in FM3A and MDA-P cells. On the other hand, the etoposide-resistant human leukemia cell line K562/MX2 and the parental cell line K562/P did not show enhanced sensitivity against etoposide or an increase in human Topoisomerase IIa mRNA. Using a recombinant adenovirus containing beta-galactosidase gene (Ad-beta-gal), K562 cells were not transducted by the recombinant adenovirus, while both etoposide-sensitive FM3A cells and etoposide resistant FvP cells were transducted by recombinant adenovirus. Ad-hTOP2alpha and etopside treatment showed reduced inoculated tumor weight in the mice. We concluded that a recombinant adenovirus containing the human Topoisomerase IIalpha gene might be a powerful tool for overcoming drug resistance in breast cancer cells, but not in leukemia cells.
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PMID:Adenovirus-mediated human topoisomerase IIalpha gene transfer increases the sensitivity of etoposide-resistant human and mouse breast cancer cells. 1607 96

The anomalous fruit extract of Gleditsia sinensis (GSE) was shown to possess anticancer potential on various solid tumour and leukaemia cell lines in vitro. We have recently demonstrated that the mitochondrial-dependent apoptotic pathway including mitochondrial membrane potential depolarization, changes in the level of reactive oxygen species and activation of caspase 3 were recruited in GSE-induced apoptosis. Whether receptor-dependent APO-1/Fas apoptotic pathway is also involved remains uncertain. Using two solid tumour cell lines, the HepG2 hepatoblastoma carcinoma cells and MDA-MB231 breast cancer cells, we demonstrated that the Fas ligand and Fas receptor protein levels did not have significant variation after GSE incubation. Caspase 8 activity increased only weakly when compared with that of caspase 3. The chrymotrypsin-like activity of proteasome was partially inhibited up to 30-40% when compared with the untreated control. Taken together, we believe that GSE- mediated apoptosis on HepG2 and MDA-MB231 carcinoma cells is mainly dictated by the mitochondrial-dependent pathway while inhibition of proteasome activity may also be involved in GSE-induced apoptosis.
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PMID:Inhibition of proteasome activity in Gleditsia sinensis fruit extract-mediated apoptosis on human carcinoma cells. 1621 Dec 65

Members of a novel series of pyrrolo-1,5-benzoxazepine (PBOX) compounds have been shown to induce apoptosis in a number of human leukemia cell lines of different haematological lineage, suggesting their potential as anti-cancer agents. In this study, we sought to determine if PBOX-6, a well characterised member of the PBOX series of compounds, is also an effective inhibitor of breast cancer growth. Two estrogen receptor (ER)-positive (MCF-7 and T-47-D) and two ER-negative (MDA-MB-231 and SK-BR-3) cell lines were examined. The 3,4,5-dimethylthiazol-2-yl-2,5-diphenyl-tetrazolium bromide (MTT) assay was used to determine reduction in cell viability. PBOX-6 reduced the cell viability of all four cell lines tested, regardless of ER status, with IC(50) values ranging from 1.0 to 2.3 microM. PBOX-6 was most effective in the SK-BR-3 cells, which express high endogenous levels of the HER-2 oncogene. Overexpression of the HER-2 oncogene has been associated with aggressive disease and resistance to chemotherapy. The mechanism of PBOX-6-induced cell death was due to apoptosis, as indicated by the increased proportion of cells in the pre-G1 peak and poly(ADP-ribose) polymerase (PARP) cleavage. Moreover, intratumoural administration of PBOX-6 (7.5 mg/kg) significantly inhibited tumour growth in vivo in a mouse mammary carcinoma model (p=0.04, n=5, Student's t-test). Thus, PBOX-6 could be a promising anti-cancer agent for both hormone-dependent and -independent breast cancers.
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PMID:The pyrrolo-1,5-benzoxazepine, PBOX-6, inhibits the growth of breast cancer cells in vitro independent of estrogen receptor status and inhibits breast tumour growth in vivo. 1621 9

Icb-1 (C1orf38) is a human gene initially described to be involved in in vitro differentiation processes of endometrial adenocarcinoma and leukemia cells. In this study, we examined the effect of interferon-gamma on icb-1alpha and beta mRNA levels in human cell lines derived from breast cancer and gynecological malignancies. Furthermore, we intended to approach icb-1 gene function by means of RNA interference (RNAi) to analyze the effect of an icb-1 knockdown on human cancer cells in vitro. Three breast cancer cell lines (MCF-7, SK-BR-3, MDA-MB-231), three ovarian cancer cell lines (SK-OV-3, OVCAR-3 and BG-1) and the endometrial adenocarcinoma cell line HEC-1-A were treated with interferon gamma and the transcript levels of icb-1 isoforms alpha and beta were assessed by means of semiquantitative real-time RT-PCR. Our data demonstrates an interferon-gamma triggered upregulation of icb-1alpha mRNA levels in all breast cancer cell lines and an increase of icb-1beta mRNA in MDA-MB-231 cells. The strongest (about 10-fold) increase of icb-1alpha and beta mRNA after treatment with interferon-gamma was observed in ovarian cancer cell line SK-OV-3. Additionally, our data demonstrates the success of a siRNA-mediated knockdown of icb-1alpha and beta mRNA levels, which resulted in a significant increase of the antiproliferative interferon-gamma effect on SK-OV-3 cells. In conclusion, we report identification of the novel interferon-gamma inducible gene icb-1 which is able to affect the response of ovarian cancer cells to this cytokine.
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PMID:Expression of icb-1 gene is interferon-gamma inducible in breast and ovarian cancer cell lines and affects the IFN gamma-response of SK-OV-3 ovarian cancer cells. 1621 72

Paclitaxel is a microtubule-stabilizing and apoptosis-inducing drug that is commonly used to treat metastatic breast cancer, although the mechanism of paclitaxel-induced apoptosis remains incompletely understood. Furthermore, adhesion molecule expression is attenuated on mouse mastocytoma and human leukemia cells that survive short-term culture in the presence of paclitaxel. In the present study we show that MDA-MB-435 human breast carcinoma cells that survived culture for 72 h in the presence of submaximal cytotoxic concentrations of paclitaxel (0.02 and 0.01 microg/ml) showed decreased expression of the adhesion molecule ICAM-1. Paclitaxel treatment of MDA-MB-435 cells was associated with the generation of reactive oxygen species (ROS), dissipation of mitochondrial transmembrane potential, and the activation of caspase-3. The antioxidant glutathione protected MDA-MB-435 cells from paclitaxel-induced cytotoxicity and reduced ICAM-1 expression. In addition, a selective inhibitor of caspase-3 (Z-DEVD-FMK), as well as a pan-caspase inhibitor (Z-VAD-FMK), partially prevented the decrease in ICAM-1 expression observed following paclitaxel treatment, but did not protect against paclitaxel-induced cytotoxicity. We conclude that the paclitaxel-induced reduction in ICAM-1 expression by MDA-MB-435 breast carcinoma cells is both ROS- and caspase-dependent, whereas paclitaxel-induced cytotoxicity is ROS-dependent and does not involve caspases. Decreased ICAM-1 expression by breast carcinoma cells that survive paclitaxel treatment may negatively impact on cytotoxic lymphocyte-mediated destruction of paclitaxel-resistant breast cancer cells in the context of chemo-immunotherapy or chemo-adoptive immunotherapy.
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PMID:Contribution of reactive oxygen species and caspase-3 to apoptosis and attenuated ICAM-1 expression by paclitaxel-treated MDA-MB-435 breast carcinoma cells. 1627 28

To investigate the possible mechanism of apoptosis induced by indole-3-acetic acid (IAA) combined with horseradish peroxidase in leukemia cell line K562, cell proliferation and apoptosis of K562 cell were examined by MTT assay and terminal deoxynucleotidyl transferase-mediated dUTP nick end labeling (TUNEL), respectively; the activity of superoxide dismutase (SOD) and the quantitative change of MDA were measured by biochemical method; changes of free radical were determined by 2, 7-dichlorofluorescin diacetate (DCFH-DA) probe with confocal microscopy. The results showed that of MTT assay and TUNEL indicated that IAA/HRP could significantly inhibit cell proliferation (P < 0.05) and induce apoptosis of K562 cell (P < 0.01), at the same time a positive correlation was found between apoptosis rate and IAA concentration (r = 0.971, P < 0.01). The activity of SOD and the quantitative of MDA increased, accompanied with a rise in IAA concentration. Results detected by DCFH-DA probe indicated that the fluorescence intensity of intracellular free radical increased, as compared with control, and a positive correlation was found. It is concluded that IAA/HRP can inhibit proliferation of K562 cells and induce K562 cell apoptosis, its mechanism may be related with the increase of intracellular free radical due to the effects of IAA/HRP.
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PMID:[Mechanism of apoptosis induced by indole-3-acetic acids combined with horseradish peroxidase in leukemia cell line K562]. 1627 39

Quercetin (QU) and trichostatin A (TSA) are promising anticancer drugs. While QU mainly exerts its anticancer activity through scavenging reactive oxygen species (ROS), the anticancer activity of TSA was attributed to its inhibition on histone deacetylases (HDAC). In the present study it was investigated, whether the combination of QU and TSA could improve their anticancer activity against human leukemia cells (HL-60). The cytotoxicity of QU and TSA increased in a time and dose-dependent manner. QU (10, 20 and 40 microM) was able to diminish the ROS generation (indicated by the level of malondialdehyde, MDA) but showed no influence on the histone acetylation in HL-60 cells; on the contrary, TSA (20, 40, 80 and 160 nM) showed no inhibition on ROS generation but significantly increased the histone acetylation, indicating the possible role of both scavenging ROS and increasing histone acetylation in the induction of cell death in HL-60 cells. This conclusion was confirmed by the findings that the combinations of QU and TSA at different concentrations could not only diminish ROS generation, but also increase histone acetylation, and hence showed more significant cytotoxicity in HL-60 cells than either of its components. Collectively, the present data indicate that a combination of QU and TSA can cooperatively kill HL-60 cells through the combination of their activities of scavenging ROS and increasing histone acetylation.
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PMID:Quercetin and trichostatin A cooperatively kill human leukemia cells. 1632 Sep 50

Cantharidin isolated from Mylabris caraganae and other insects has been used as an anti-cancer drug in China for many years. However, its toxicity on the renal system and suppression effect on bone marrow limits its usage clinically. Based on the core structure of cantharidin, we have chemically synthesized two cantharidin analogues (compounds 2 and 3). The cytotoxic activity of these analogues was demonstrated on the Hep3B hepatocellular carcinoma, MDA-MB231 breast cancer, A549 non-small cell lung carcinoma and KG1a acute myelogenous leukaemia (AML) cell lines by monitoring the intracellular adenosine triphosphate level. Morphological changes in these cancer cell lines, including cell shrinkage and loss of adherent potential, were readily observed. By making use of the KG1a AML cells as a test model, we further found that mitochondrial membrane potential depolarization and reduction of intracellular bcl-2 anti-apoptotic protein level were involved. These resulted in the activation of caspase 3 protease activity and oligonucleosomal length DNA fragment formation as detected by both time resolved fluorescence technology-based caspase activity assay and TdT-mediated dUTP nick end-labelling assay.
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PMID:Induction of apoptosis on carcinoma cells by two synthetic cantharidin analogues. 1632 24

The effective microorganism fermentation extract (EM-X, the first generation) was claimed to possess strong anti-oxidation property. On the other hand, we have shown that the second generation of the effective microorganism fermentation extract (EM-X2) possessed growth inhibition on human cancer cells involving MDA-MB231 breast cancer and K-562 chronic myelogenous leukaemia cells. Elevation of super oxide dismutase activity from EM-X2 treated cancer cell extract was observed. However, the possible anti-cancer activity of the first generation of the EM-X was not reported. Here we demonstrate that the concentrated form of the EM-X from its original fluid also possess antiproliferation ability together with induction of apoptosis on the human cancer cell lines including Hep3B hepatocellular carcinoma (HCC) and KG1a acute myelogenous leukaemia (AML). Similar effect could also be demonstrated on primary cultured bone marrow samples isolated from patients with AML. Morphological inspection revealed that common apoptotic feature was found on these concentrated EM-X treated cancer cells. Both the anchorage-dependent clonogenicity assay on Hep3B HCC and methyl-cellulose colony formation assay on KG1a cells and bone marrow cells from AML patients further revealed the ability of the concentrated EM-X on reducing their colony formation ability. Incubating KG1a with concentrated EM-X readily induced apoptosis as demonstrated by flow cytometric analysis. Interestingly, few growth inhibition effect of the concentrated EM-X was observed on both the SV40 transformed THLE-2 liver epithelial cells and primary cultured non-malignant haematological disordered bone marrow. Collectively, this concentrated EM-X is effective in inducing cell death and reducing the regeneration potential of both Hep3B HCC and KG1a AML cells in vitro.
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PMID:Apoptotic potential of the concentrated effective microorganism fermentation extract on human cancer cells. 1639 27

Constitutive nuclear factor-kappaB (NF-kappaB) activity plays a crucial role in the development and progression of lymphoma, leukemia, and some epithelial cancers. Given the contribution of NF-kappaB in carcinogenesis, a novel approach that interferes with its activity might have therapeutic potential against cancers that respond poorly to conventional treatments. Here, we have shown that a new IkappaB kinase beta inhibitor, IMD-0354, suppressed the growth of human breast cancer cells, MDA-MB-231, HMC1-8, and MCF-7, by arresting cell cycle and inducing apoptosis. In an electrophoretic mobility shift assay and a reporter assay, IMD-0354 abolished the NF-kappaB activity in MDA-MB-231 cells in a dose-dependent manner. In the cells incubated with IMD-0354, cell cycle arrested at the G0-G1 phase and apoptotic cells were increased. The expression of some cell cycle regulatory molecules and antiapoptotic molecules was suppressed in cells treated with IMD-0354. On the other hand, cyclin-dependent kinase suppressor p27Kip1 was up-regulated by the addition of IMD-0354. Daily administration of IMD-0354 inhibited tumor expansion in immunodeficient mice into which MDA-MB-231 cells were transplanted. These results indicate that NF-kappaB may contribute to cell proliferation through up-regulation of cell cycle progression; accordingly, inhibition of NF-kappaB activity might have a therapeutic ability in the treatment of human breast cancers.
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PMID:A new IkappaB kinase beta inhibitor prevents human breast cancer progression through negative regulation of cell cycle transition. 1639 57


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