Gene/Protein Disease Symptom Drug Enzyme Compound
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Query: UMLS:C0023473 (chronic myeloid leukemia)
 18,916 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

This study was aimed to investigate the role of mitochondria pathway in signal transduction of chronic myeloid leukemia (CML). After bcr3/abl2 antisense oligodeoxynucleotide (ASO) was introduced into CML cell line K562 cells by liposomal transfection, the cell viability was detected by MTT assay, the cell apoptosis was determined by flow cytometry (FCM), the mitochondrial membrane potential (DeltaPsi) was labeled by Rhodamine 123 and examined by FCM, and the expression of mitochondrial apoptosis signal transduction pathway related proteins cytochrome C was analyzed by Western blot. The results showed that after K562 cells were exposed to 2 micromol/L of bcr3/abl2 ASO for 24 hours, bcr3/abl2 ASO significantly inhibited cell viability with inhibitory rate of 65.7%, induced the apoptosis of K562 cell line with apoptotic rate of 16.9%, and decreased mitochondrial Deltapsi of K562 cells with the reducing rate of 38.33%, enhanced the expression of cytochrome C with increase of optical density value from 2.33 +/- 0.3 to 4.78 +/- 0.1 by laser photometric scanning. It is concluded that mitochondria pathway plays an important role in signal transduction of chronic myeloid leukemia by directing apoptotic signal transduction.
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PMID:[Role of mitochondria pathway in signal transduction of chronic myeloid leukemia]. 1937 50

Comparison of binding properties of a series of monomethine cyanine derivatives to ds-DNA and ds-RNA revealed significant impact of the properties of substituent attached to the longer axis of aromatic core. Namely, it seems that only compounds 7, 8 characterised by length of longer axis not exceeding the length of longer axis of basepairs could intercalate into ds-DNA and ds-RNA, while the increased substituent length and additional possibility of hydrogen bonds formation directed binding of 1-6 into ds-DNA minor groove. Consequent ds-RNA over ds-DNA selectivity of 7 and 8 is the most appealing and rather rare property among small molecules. The interactions of 1-8 with ss-RNA were strongly dependent on both, structure of compound and base composition of RNA. The cytotoxicity screening of compounds 1-8 by MTT test revealed considerable antiproliferative activity against solid tumours and especially toward haematological malignancies (IC(50)=0.001-6.6 microM), whereby normal human aortic endothelial cells (HAEC) were significantly less affected (IC(50)=1-200 microM). The cells of chronic myeloid leukaemia in blast crisis (K562) were especially sensitive to all tested compounds (IC(50)=0.001-0.6 microM), while normal lymphocytes were more resistant (IC(50)=0.01-1 microM). Results of uptake and intracellular distribution of compounds 1 and 2 in the living cells showed that they do not bind primarily to nuclear DNA but their fluorescence is scattered through the whole cells. A detailed mechanism of antitumor activity of tested molecules remains to be investigated.
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PMID:Minor structural differences of monomethine cyanine derivatives yield strong variation in their interactions with DNA, RNA as well as on their in vitro antiproliferative activity. 1947 32

The S-methyl-thiosemicarbazones of the 2-hydroxy-R-benzaldehyde (R = H, 3-OH 3-OCH(3) or 4-OCH(3)) reacted with the corresponding aldehydes in the presence of FeCl(3) and NiCl(2). New ONNO chelates of iron(III) and nickel(II) with hydroxy- or methoxy-substituted N(1),N(4)-diarylidene-S-methyl-thiosemicarbazones were characterized by means of elemental analysis, conductivity and magnetic measurements, UV-Vis, IR and (1)H-NMR spectroscopies. Cytotoxic activities of the compounds were determined using K562 chronic myeloid leukemia and ECV304 human endothelial cell lines by MTT assay. It was determined that monochloro N(1)-4-methoxysalicylidene-N(4)-4-methoxysalicylidene-S-methyl-thiosemicarbazidato-iron(III) complex showed selective anti-leukemic effects in K562 cells while has no effect in ECV304 cells in the 0.53 microg/ml (IC(50)) concentrations. Also, some methoxy-substituted nickel(II) chelates exhibit high cytotoxic activity against both of these cell lines in low concentrations. Cytotoxicity data were evaluated depending on cell lines origin and position of the substituents on aromatic rings.
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PMID:Cytotoxic activities of new iron(III) and nickel(II) chelates of some S-methyl-thiosemicarbazones on K562 and ECV304 cells. 1949 62

Imatinib mesylate is effective against Ph chromosome-positive leukemia; however, resistance has been reported. High expression of bcr-abl in mRNA and protein levels, and other alterations were found in patients who experienced imatinib treatment failures and thus it is important to design alternative treatment strategies. The aim of this study was to evaluate the in vitro effect of berbamine, on imatinib-resistant chronic myelogenous leukemia (CML) K562 (K562-r) cells, and explore the mechanisms. The growth of K562-r cells was examined using the 3-(4,5-dimethylthiazol-2yl)-2,5-diphenyl-tetrazolium bromide (MTT) assay. Morphological analysis and DNA agarose electrophoresis were used to detect apoptosis in K562-r cells, and the extent of the cells in the sub-G1 cell cycle phase was measured using flow cytometry. The expression levels of BCR-ABL, phospho-BCR-ABL, and nuclear factor kappaB (NF-kappaB), IkappaBalpha, phospho-IkappaBalpha, IkappaB kinases alpha(IKKalpha), and Survivin were determined by Western blot. bcr-abl mRNA expression was determined by RT-PCR. MTT assays indicated that berbamine significantly inhibited the proliferation of K562-r cells. Cells with characteristics of apoptosis were confirmed by morphology examination and DNA agarose electrophoresis and percentage of apoptosis were increased after treatment with berbamine. The results also showed that berbamine was able to down-regulate BCR-ABL and phospho-BCR-ABL proteins by affecting bcr-abl mRNA expression and decrease expression of nuclear NF-kappaB, phospho-IkappaBalpha, IKKalpha, and Survivin. Collectively, berbamine could inhibit the proliferation of K562-r cells and induce apoptosis. The mechanisms may be related at least in part, to inhibit BCR-ABL and its downstream NF-kappaB signaling. Berbamine may provide an alternative candidate for the treatment of patients with CML resistant to imatinib therapy.
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PMID:The antiproliferation effect of berbamine on k562 resistant cells by inhibiting NF-kappaB pathway. 1954 6

A novel mannose-binding lectin (designated CML) was isolated from Clematis montana Buch.-Ham stem (Ranunculaceae) using ion exchange and gel filtration chromatographies on DEAE-Sepharose and Sephacryl S-100. The purified C. montana lectin was a homodimer of 11,968.9 Da subunits as determined by gel filtration and MS. The hemagglutinating activity of CML was inhibited by branched oligomannosides. The N-terminal 15-amino acid sequence of CML, DNVKYSGQVKNTGSA, has not been reported for other lectins. Also, the peptide mass fingerprinting assay confirmed that there is no match result of similar plant lectins for CML, indicating CML may be a novel plant lectin. CML showed marked antiviral activity against various viruses in cell culture. Subsequently, CML was also found to exhibit remarkable inhibitory effect on L929, HeLa, MCF7 and HepG2 cells. Furthermore, CML specially induced L929 cell apoptosis in dose-dependent manner as evidenced by MTT, fluorescent microscopy, LDH activity-based cytotoxicity assays and DNA ladder. Moreover, due to both caspase inhibitors and Western blot analyses, caspase was also found to play the important role in the potential apoptotic mechanism of CML. When the carbohydrate-binding site was fully inhibited by sugars, cytotoxicity was abruptly decreased and apoptotic phenomenon in L929 cells was not observed, suggesting a significant correlation between mannose-binding-specific activity and the antineoplastic mechanism.
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PMID:Clematis montana lectin, a novel mannose-binding lectin from traditional Chinese medicine with antiviral and apoptosis-inducing activities. 1957 2

Emodin (1,3,8-trihydroxy-6-methyl-anthraquinone), a natural anthraquinone derivative isolated from Rheum palmatum L, has been reported to exhibit anti-cancer effect on several human cancers such as liver cancers and lung cancers. However, the molecular mechanisms of emodin-mediated tumor regression have not been fully defined. Our preliminary study showed that emodin had highly cytotoxic effect on human chronic myeloid leukemia K562 cell lines. This study was performed to investigate the anti-tumor effect of emodin in human K562 cell line in vitro and in vivo. The MTT data showed the inhibition on growth of K562 cells following emodin treatment. Flow cytometry showed that the cell cycle of K562 cells was arrested in G(0)/G(1) phase. Through Western blot analysis, we found that the apoptosis-related protein Bcl-2 was decreased in a dose-dependent manner and the Bax was increased after emodin treatment. Moreover, activations of caspase-3, -8 and -9 were demonstrated in vitro and in vivo. The increased Bax concurrent with the decreased of Bcl-2 indicated that emodin treatment might result in apoptosis of K562 cells. The cell apoptosis was also directly demonstrated by Annexin V-FITC, and DNA fragmentation assay. Additionally, the tumoricidal effect of emodin was measured using a xenograft nude mice model. We found that, after inoculated with the K562 cells, the nude mice treated with emodin showed a significant decrease of tumor volume and tumor weight in comparison to the control. Emodin could cause the regression of tumor. Both in vitro and in vivo studies suggest that emodin can be developed as a promising anti-chronic myeloid leukemia drug.
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PMID:Anti-tumor activity of emodin against human chronic myelocytic leukemia K562 cell lines in vitro and in vivo. 1985 84

In comparison with four tumor cell lines and three non transformed cell types, chronic myeloid leukemia K562 cells were selectively sensitive to proliferation inhibition by the oxoindole derivative XJW20, as determined by the MTT assay. Further investigation revealed that XJW20 selectively induced G2/M arrest and apoptosis in K562 cells. At the molecular level, XJW20-induced G2/M arrest was accompanied by up-regulation of cyclin B1 and phospho (p)-Cdc25C (Ser216) and down-regulation of CDK1. There is no change in the expression of CDK2. The increased apoptotic activity by XJW20 was characterized by an increase in reactive oxygen species (ROS) generation, the mitochondrial transmembrane potential (DeltaPsi(m)) dissipation, cytochrome C releasing, apoptotic nuclei (AO/EB double staining) and nuclei condensation (DAPI-staining). The down-regulation of phosphorylated ERK was also found in XJW20-treated K562 cells. These molecular events induced by XJW20 may provide insight into the mechanism of action that led to growth arrest and apoptosis.
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PMID:XJW20, a novel oxoindole derivative, induces G2/M arrest and apoptosis selectively in K562 leukemia cell line. 1988 35

The study was aimed to investigate the effects of emodin on proliferation inhibition and apoptosis induction in human chronic myeloid leukemia cell line K562 cells, and to explore the role of P210 protein and activation of caspase 3 in these processes. K562 cells were exposed to emodin at different doses. The proliferation inhibition was detected by MTT assay and colony formation test. The ability of emodin to induce apoptosis and DNA fragmentation were examined by flow cytometry. The expressions of P210, procaspase-3 and PARP protein were determined by Western blot. The results indicated that the emodin remarkably inhibited the K562 cell proliferation, with IC(50) value of 38.25 micromol/L after treatment for 48 hours. Meanwhile induced apoptosis, Annexin V-FITC positive cells, sub-G(1) apoptotic peak and DNA fragmentation in K562 cells confirmed that emodin induced apoptosis in K562 cells in dose-dependent manner. Western blot results showed that emodin inhibited phosphorylation of P210 protein in K562 cells and down-regulated the expression levels of P210. The procaspase-3 level in treated K562 cells decreased with increased expressions of PARP in time-dependent manner. It is concluded that the emodin efficiently inhibits growth and induces apoptosis of K562 cells, while the inhibition of phosphorylation of P210 protein, down-regulation of P210 protein expression and activation of caspase-3 may be involved in these processes.
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PMID:[Effect of emodin on proliferation inhibition and apoptosis induction in leukemic K562 cells]. 2003 Sep 21

A water-soluble Pd(II) complex (2,2'-bipyridinglycinato Pd(II) nitrate) has been synthesized and characterized. The effect of synthesized complex on the carrier model protein structure and cell proliferation was investigated. Whey carrier protein beta-lactoglobulin-B (BLG-B) and chronic myelogenous leukemia cell line K562 were the targets. Fluorescence and CD instruments were used to assess effect of the complex on the protein structure at different temperatures. Growth inhibitory and apoptotic effect of the Pd(II) complex toward the cancer cells was measured using 3-(4,5-dimethylthiazol-2-yl)-2,5-diphenyltetrazolium bromide (MTT) assay and flow cytometry. This complex exhibited potent cytotoxic properties against chronic myelogenous leukemia cell line K562. The cells showed different sensitivity to complex. Cytotoxic studies shown that Pd(II) complex induced apoptosis of K562 cells in a concentration and time dependent manner. Then, it might be concluded that Pd(II) complex is a promising antiproliferative agent and should execute its biological effects by inducing apoptosis. Results of fluorescence studies revealed that Pd(II) complex can quench the intrinsic fluorescence emission of the protein at different temperatures. The far- and near-UV CD studies displayed that the Pd(II) complex induces changes in the secondary and tertiary structures of BLG-B at different temperatures. The biological significance of this work is evident since BLG serves as a carrier molecule for several antitumor compounds. Therefore, the interaction of the Pd(II) complex (with antitumor activity) can provide useful information to better design metal anticancer complexes with fewer side effects.
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PMID:Design, synthesis, and biological evaluation of a new palladium(II) complex: beta-lactoglobulin and K562 as targets. 2017 5

This study was aimed to investigate the anti-angiogenesis of IFN-alpha2b in chronic myeloid leukemia (CML) in vitro by using K562 cell line and human umbilical vein endothelial cells (HUVEC). The levels of vascular endothelial growth factor (VEGF) and basic fibroblast growth factor (bFGF) in culture supernatant of K562 cells were determined by ELISA; the expressions of VEGF and bFGF mRNA after treating K562 cells with 10(3), 10(2) and 10 U/ml IFN-alpha2b for 24, 36, 48 hours were detected by real-time RT-PCR; the effects of K562 cell culture supernatant and IFN-alpha2b on proliferation, migration and differentiation of HUVEC in vitro were assayed by MTT, Transwell chamber and tubule formation assay respectively. The results showed that the K562 cells expressed and secreted VEGF and bFGF. The culture supernatant of K562 cells significantly promoted the proliferation, migration and tubule formation of HUVEC in vitro in a concentration-dependent manner. After treating K562 cells with IFN-alpha2b 10 U/ml for 24, 36 and 48 hours, the expression levels of VEGF and bFGF mRNA were 1.64+/-0.18, 1.49+/-0.14, 1.31+/-0.05 and 1.53+/-0.10, 1.29+/-0.15, 0.79+/-0.13 respectively (p=0.002), but the expression levels of VEGF and bFGF mRNA were not significantly different along with increasing of IFN-alpha2b concentration. It is concluded that the angiogenesis exists in CML. The K562 cell expresses and secrets VEGF and bFGF, which promotes the proliferation, migration and differentiation of HUVEC. The IFN-alpha2b displays anti-angiogenesis by inhibiting the proliferation, migration and tubule formation in vitro of HUVEC and down regulating the expression of VEGF and bFGF mRNA.
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PMID:[Anti-angiogenesis of interferon-alpha2b in chronic myeloid leukemia in vitro]. 2041 54


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