HL-60 Cells: A promyelocytic cell line derived from a patient with ACUTE PROMYELOCYTIC LEUKEMIA. HL-60 cells lack specific markers for LYMPHOID CELLS but express surface receptors for FC FRAGMENTS and COMPLEMENT SYSTEM PROTEINS. They also exhibit phagocytic activity and responsiveness to chemotactic stimuli. (From Hay et al., American Type Culture Collection, 7th ed, pp127-8)Leukemia, Promyelocytic, Acute: An acute myeloid leukemia in which abnormal PROMYELOCYTES predominate. It is frequently associated with DISSEMINATED INTRAVASCULAR COAGULATION.Dimethyl Sulfoxide: A highly polar organic liquid, that is used widely as a chemical solvent. Because of its ability to penetrate biological membranes, it is used as a vehicle for topical application of pharmaceuticals. It is also used to protect tissue during CRYOPRESERVATION. Dimethyl sulfoxide shows a range of pharmacological activity including analgesia and anti-inflammation.Cell Differentiation: Progressive restriction of the developmental potential and increasing specialization of function that leads to the formation of specialized cells, tissues, and organs.Tretinoin: An important regulator of GENE EXPRESSION during growth and development, and in NEOPLASMS. Tretinoin, also known as retinoic acid and derived from maternal VITAMIN A, is essential for normal GROWTH; and EMBRYONIC DEVELOPMENT. An excess of tretinoin can be teratogenic. It is used in the treatment of PSORIASIS; ACNE VULGARIS; and several other SKIN DISEASES. It has also been approved for use in promyelocytic leukemia (LEUKEMIA, PROMYELOCYTIC, ACUTE).Leukemia, Myeloid, Acute: Clonal expansion of myeloid blasts in bone marrow, blood, and other tissue. Myeloid leukemias develop from changes in cells that normally produce NEUTROPHILS; BASOPHILS; EOSINOPHILS; and MONOCYTES.Granulocytes: Leukocytes with abundant granules in the cytoplasm. They are divided into three groups according to the staining properties of the granules: neutrophilic, eosinophilic, and basophilic. Mature granulocytes are the NEUTROPHILS; EOSINOPHILS; and BASOPHILS.Tetradecanoylphorbol Acetate: A phorbol ester found in CROTON OIL with very effective tumor promoting activity. It stimulates the synthesis of both DNA and RNA.Tumor Cells, Cultured: Cells grown in vitro from neoplastic tissue. If they can be established as a TUMOR CELL LINE, they can be propagated in cell culture indefinitely.Leukemia, Myeloid: Form of leukemia characterized by an uncontrolled proliferation of the myeloid lineage and their precursors (MYELOID PROGENITOR CELLS) in the bone marrow and other sites.Cell Line: Established cell cultures that have the potential to propagate indefinitely.Calcitriol: The physiologically active form of vitamin D. It is formed primarily in the kidney by enzymatic hydroxylation of 25-hydroxycholecalciferol (CALCIFEDIOL). Its production is stimulated by low blood calcium levels and parathyroid hormone. Calcitriol increases intestinal absorption of calcium and phosphorus, and in concert with parathyroid hormone increases bone resorption.Apoptosis: One of the mechanisms by which CELL DEATH occurs (compare with NECROSIS and AUTOPHAGOCYTOSIS). Apoptosis is the mechanism responsible for the physiological deletion of cells and appears to be intrinsically programmed. It is characterized by distinctive morphologic changes in the nucleus and cytoplasm, chromatin cleavage at regularly spaced sites, and the endonucleolytic cleavage of genomic DNA; (DNA FRAGMENTATION); at internucleosomal sites. This mode of cell death serves as a balance to mitosis in regulating the size of animal tissues and in mediating pathologic processes associated with tumor growth.Leukemia: A progressive, malignant disease of the blood-forming organs, characterized by distorted proliferation and development of leukocytes and their precursors in the blood and bone marrow. Leukemias were originally termed acute or chronic based on life expectancy but now are classified according to cellular maturity. Acute leukemias consist of predominately immature cells; chronic leukemias are composed of more mature cells. (From The Merck Manual, 2006)N-Formylmethionine Leucyl-Phenylalanine: A formylated tripeptide originally isolated from bacterial filtrates that is positively chemotactic to polymorphonuclear leucocytes, and causes them to release lysosomal enzymes and become metabolically activated.

*  Crocin Exhibits Antitumor Effects on Human Leukemia HL-60 Cells In Vitro and In Vivo
... amount of apoptotic cell/total cell examined) × 100%.. 2.4. Cell Cycle Analysis. HL-60 cells were treated with different ... Cell Proliferation Assay. Cell proliferation was determined by using MTT assay. Briefly, HL-60 cells were treated with crocin ( ... Cell Line and Treatment. Human leukemia HL-60 cells were gifted from the Institute of Hematology and Blood Diseases Hospital, ... After 48 h, cells were harvested and fixed in 70% ethanol at 4°C overnight. Fixed cells were stained with 5 μL PI for 20 min on ...
  https://www.hindawi.com/journals/ecam/2013/690164/
*  Lantadene A induced apoptosis in human leukemia HL-60 cells | Clinical Cancer Research
LA significantly inhibited cell proliferation of HL-60 cells and induced cell apoptosis through down regulating Bcl-2 and up ... The effect of LA on cell proliferation of HL-60 cancer cells were determined by MTT assay. The morphological effects of LA ... Flow cytometry was carried out to observe changes in cell-cycle distribution of the cells. The expression of Bcl-2 and Bax ... Flow cytometric analysis showed suppressed cell proliferation associated with cell cycle arrest in the G0/G1 phase. ...
  http://clincancerres.aacrjournals.org/content/13/22_Supplement/B36
*  The protective role of HSP on HL-60 cell apoptosis | Biochemical Society Transactions
The protective role of HSP on HL-60 cell apoptosis. B.T. Doyle, H. Hurley, A.J. O'Neill, P. Newsholme, J.M. Fitzpatrick, R.W.G. ... The protective role of HSP on HL-60 cell apoptosis. B.T. Doyle, H. Hurley, A.J. O'Neill, P. Newsholme, J.M. Fitzpatrick, R.W.G. ... The protective role of HSP on HL-60 cell apoptosis Message Subject (Your Name) has forwarded a page to you from Biochemical ...
  http://www.biochemsoctrans.org/content/29/5/A110.3
*  Induction of differentiation in acute promyelocytic leukemia cells (HL-60) by the verticillin derivative Sch 52900
... Erkel, G; ... Section C: A Journal of Biosciences}, title = {Induction of differentiation in acute promyelocytic leukemia cells (HL-60) by ... The HL-60 cell line, derived from a patient with acute promyelocytic leukemia, is a widely used model system to study the ... The HL-60 cell line, derived from a patient with acute promyelocytic leukemia, is a widely used model system to study the ...
  https://lup.lub.lu.se/search/publication/326269
*  Translocation of Protein Phosphatase 1 Catalytic Subunits during 1,25-Dihydroxyvitamin D3-induced Monocytic Differentiation of...
Calyculin-A augmented the 1,25(OH)2D3-induced differentiation of the cells. Treatment of the cells with 1,25(OH)2D3 led to a ... The correlation between phenotypic and functional changes of HL-60 cells on the one hand and subcellular redistribution of PP1- ... 25-Dihydroxyvitamin D3-induced Monocytic Differentiation of HL-60 Cells. Serdar B. Omay, Hitoshi Ogasawara, Hideki Toyoda, ... 25-Dihydroxyvitamin D3-induced Monocytic Differentiation of HL-60 Cells. Serdar B. Omay, Hitoshi Ogasawara, Hideki Toyoda, ...
  http://cancerres.aacrjournals.org/content/55/4/774
*  Ceramide Reduction and Transcriptional Up-Regulation of Glucosylceramide Synthase through Doxorubicin-Activated Sp1 in Drug...
Effects of DOX on cell viability, cell growth, and induction of apoptosis in Sp1 decoy ODN-transfected HL-60/ADR cells. After ... In A and B, cell viability was calculated as a percentage of viable cells (versus total number of cells), after viable cell ... The number of subdiploid cells (apoptotic cells) and cell cycle phases with more than diploid DNA content (nonapoptotic cells) ... for 46 hours significantly decreased cell viability and cell growth as judged by viable cell numbers in Sp1 ODN-transfected HL- ...
  http://cancerres.aacrjournals.org/content/64/17/6271
*  Induction of Differentiation of HL-60 Cells by Dimethyl Sulfoxide: Evidence for a Stochastic Model Not Linked to the Cell...
Induction of differentiation of the human promyelocytic leukemia cell line HL-60 by dimethyl sulfoxide (Me2SO) was analyzed to ... The effect of Me2SO was not altered when incubated with cells at different phases of the cell cycle. Finally, even ... a linear rise in the percentage of differentiated cells was observed. The sensitivity to Me2SO of HL-60 cells synchronized by ... The data are consistent with a stochastic model of induction to differentiation without having any linkage to the cell cycle. ...
  http://cancerres.aacrjournals.org/content/42/2/445
*  Stimulation of hydrogen peroxide production by drinking water contaminants in HL-60 cells sensitized by retinoic acid. | Base...
However, in HL-60 cells sensitized by pretreatment of 10 nM retinoic acid (RA) for 12 h, chloroform induced a significant ... Stimulation of hydrogen peroxide production by drinking water contaminants in HL-60 cells sensitized by retinoic acid. R f. ... These results indicate that chloroform and trichloroethylene may stimulate H2O2 production in HL-60 cells sensitized by ... In PMN and RA-untreated HL-60 cells chloroform did not significantly affect H2O2 levels. ...
  http://www.bdsp.ehesp.fr/Base/173245/
*  Increased expression of the inositol 1,4,5-trisphosphate receptor in human leukaemic (HL-60) cells differentiated with retinoic...
Me2SO the cells differentiate within 5-7 days into cells resembling neutrophils in both structure and function. Treated cells ... The Ins(1,4,5)P3 receptor was examined in human promyelocytic leukaemic cells (HL-60) and in HL-60 cells differentiated towards ... Concomitant with HL-60 cell differentiation, the maximal [3H]Ins(1,4,5)P3 binding in membranes increases 3-4-fold, with no ... The results suggest that there is an absolute increase in the level of the InsP3 receptor during HL-60 cell differentiation and ...
  http://www.biochemj.org/content/280/1/205
*  Cell proliferation and CD11b expression are controlled independently during HL60 cell differentiation initiated by 1,25 alpha...
... a burst of approximately three shortened cell cycles ('maturation divisions') precedes exit from cell cycle and completion of ... Elutriation was used to isolate small HL60 cells (almost all in G1) and larger cells (in G1 and S phases) from unsynchronized ... Cell proliferation and CD11b expression are controlled independently during HL60 cell differentiation initiated by 1,25 alpha- ... induces HL60 cells to differentiate to monocytes, a burst of approximately three shortened cell cycles ("maturation divisions ...
  http://www.biomedsearch.com/nih/Cell-proliferation-CD11b-expression-are/11339831.html
*  Incomplete functional differentiation of HL-60 leukemic cells by synthetic lipopeptides. Partial inhibition by pertussis toxin...
In Pam3CysSer(Lys)4-differentiated HL-60 cells, the responsiveness to the [Ca2+]i-increasing agonists, N-formyl-L-methionyl-L- ... J. 267, 795-802). We studied the effects of lipopeptides on differentiation of HL-60 leukemic cells. Pam3CysSer(Lys)4 enhanced ... Pam3CysSer(Lys)4 did not inhibit proliferation of HL-60 cells but decreased transferrin receptor expression and increased C3bi ... Our results suggest that (a) Pam3CysSer(Lys)4 induces incomplete functional differentiation of HL-60 cells through a mechanism ...
  https://epub.uni-regensburg.de/23223/
*  Hypericium perforatum extract (St. John s Wort) and hypericin induce apoptosis in leukemic HL-60 cells by effecting h-TERT...
was found to have cytotoxicity in HL-60 cells in time and dose dependent manner between the doses of 1nM to 100 μM with IC50 ... John s Wort) and hypericin induce apoptosis in leukemic HL-60 cells by effecting h-TERT activity. Kezban P nar zen1, Fahri ahin ... John s Wort) and hypericin induce apoptosis in leukemic HL-60 cells by effecting h-TERT activity. Turk J Hematol. 2007; 24(3): ... Apoptosis as an underlying mechanism of this cytoxocity was shown in HL-60 cells after incubation with IC50 dose of hypericin ...
  http://www.tjh.com.tr/jvi.aspx?pdir=tjh&plng=eng&un=TJH-35744
*  Phosphorylation of a 72-kDa nucleoprotein (NP-72) in HL-60 cells is mediated by the double-stranded DNA-dependent protein...
The 300-kD form of DNA-PK was only detected in TPA-treated nuclear extracts, raising the possibility that cell differentiation ... Nuclear extracts prepared from human leukemic cells grown in the presence of cell differentiation-inducing agents showed a ... Phosphoamino acid analysis showed serine (60%) and threonine (40%) residues to be the phosphate acceptors. Western blot ... Nuclear extracts prepared from human leukemic cells grown in the presence of cell differentiation-inducing agents showed a ...
  https://www.semanticscholar.org/paper/Phosphorylation-of-a-72-kDa-nucleoprotein-
*  Characteristics of doxorubicin-selected multidrug-resistant human leukemia HL60 cells with tolerance to arsenic trioxide and...
Drug‑resistance in these cells may be due to surviving chemoresistant LSCs in the HL60 population, which have been subjected ... Unlike other recognized chemoresistant leukemia cell lines, HL60/RS cells were also strongly cross‑resistant to arsenic ... The drug‑resistant HL60/RS cells exhibited 85.68‑fold resistance to doxorubicin and were cross‑resistant to other ... The cells over‑expressed the transporters P‑glycoprotein, multidrug‑resistance‑related protein 1 and breast‑cancer‑resistance ...
  https://www.spandidos-publications.com/ol/15/1/1255/abstract
*  Andrographolide Modulate some Toll-like Receptors and Cytokines Expressions in HL-60 Cell Line | MedCrave
In vitro cell toxicity study. Human Promyelocytic leukemic cell line (HL-60, NCCS Pune, India) was maintained in 10% serum ... In cell cytotoxity experiment, 10 µM andrographolide hat no effects on viability HL-60 cells and its calculated IC50 for 50% ... on cell viability by MTT assay. In short, the viability of HL-60 cells were quantified in terms of mitochondrial metabolic ... MTT Cell Growth Assay Kit, Millipore, USA). After 24 h pre-incubations, WST-1 was added to the cells and further incubated for ...
  http://googlescholar.medcraveonline.com/scholars/article_fulltext/1612
*  A new daunomycin-peptide conjugate : synthesis, characterization and the effect on the protein expression profile of HL-60...
RP-HPLC data indicate that the conjugate is stable at least for 24 h in the pH 2.5-7.0 range of buffers, as well as in cell ... RP-HPLC data indicate that the conjugate is stable at least for 24 h in the pH 2.5-7.0 range of buffers, as well as in cell ... The in vitro cytostatic effect and cellular uptake of Dau═Aoa-LTVSPWY-NH2 conjugate were studied on various human cancer cell ... The in vitro cytostatic effect and cellular uptake of Dau═Aoa-LTVSPWY-NH2 conjugate were studied on various human cancer cell ...
  https://kops.uni-konstanz.de/handle/123456789/17240
*  Epicatechin acts synergistically with curcumin-induced cytogenotoxic effect in acute promyelocytic leukemia HL-60 cell line
The cells were incubated with ethanol for 24 h at -20 °C and then washed twice with 1% BSA in PBS. Next, HL-60 cells (0.4 × 106 ... Cells of the HL-60 line obtained from the American Type Culture Collection (ATCC, European branch in UK) were cultured in RPMI- ... The flavonoids we investigated did not significantly modify the effect of curcumin on cell cycle in HL-60 cells (data not shown ... Cell staining and analysis for γH2AX and the cell cycle. Phosphorylated histone H2AX (γ-H2AX) was detected as a marker of DNA ...
  http://jumdjournal.net/article/view/2085
*  Cytotoxic Activity of Mangosteen (Garcinia mangostana L.) Peel Extract and α-Mangostin toward Leukemia Cell Lines (HL-60 and K...
Cytotoxic Activity of Mangosteen (Garcinia mangostana L.) Peel Extract and α-Mangostin toward Leukemia Cell Lines (HL-60 and K- ... The MPE and α-mangostin revealed higher mortality toward leukemia cell lines rather than toward lymphocyte cells, with more ... Peel Extract and α-Mangostin toward Leukemia Cell Lines (HL-60 and K-562). Journal of Natural Remedies, 16 (2). pp. 53-59. ISSN ... and α-mangostin against two leukemia cell lines (HL-60 and K-562) and the normal lymphocyte cells from two different donors. ...
  http://repository.maranatha.edu/21263/
*  HL60 - Wikipedia
... cell line has been used for laboratory research on how certain kinds of blood cells are formed. HL-60 proliferates continuously ... The cell line was derived from a 36-year-old woman with acute promyelocytic leukemia at MD Anderson Cancer Center. HL-60 cells ... 1979). "Characterization of the continuous, differentiating myeloid cell line (HL-60) from a patient with acute promyelocytic ... which are expressed on cell surface. The requirement for insulin and transferrin is absolute, as HL-60 proliferation ...
  https://en.wikipedia.org/wiki/HL60
*  Cytochalasin B - Wikipedia
found that CB causes multinucleation in cells and significantly affects cell motility. The multinucleated cells probably arise ... Tanaka, Y.; Yoshihara, K.; Tsuyuki, M.; Kamiya, T. (1994). "Apoptosis Induced by Adenosine in Human Leukemia HL-60 Cells". ... Cells treated with cytochalasin B and control group cells could not be distinguished. This indicated, that CB has no ... These are small nuclei containing one chromosome or part of a chromosome which did not get to one of the cell poles during cell ...
  https://en.wikipedia.org/wiki/Cytochalasin_B
*  Formyl peptide receptor 2 - Wikipedia
Accordingly, the human leukocyte cell line, HL-60 promyelocytes (which do not respond to FMLP), was purposely differentiated to ... and immature dendritic cells; vascular endothelial cells; neural tissue glial cells, astrocytes, and neuroblastoma cells; liver ... lymphocyte T cells and B cells; tissue Mast cells, macrophages, fibroblasts, ... Murphy PM, Gallin EK, Tiffany HL, Malech HL (Feb 1990). "The formyl peptide chemoattractant receptor is encoded by a 2 kilobase ...
  https://en.wikipedia.org/wiki/Formyl_peptide_receptor_2
*  Tectorigenin - Wikipedia
Induces Differentiation and Apoptosis in Human Promyelocytic Leukemia HL-60 Cells. Lee Kyung-Tae, Sohn Il-Cheol, Kim Young-Kwan ...
  https://en.wikipedia.org/wiki/Tectorigenin
*  Type 2 Nutrition: June 2014
Better control means the surviving beta cells of the pancreas get a rest. An A1c of 7.0% is equivalent to an estimated average ... Chapel Hill). A controversial counter message, it focuses, as it should in my opinion, on "lifestyle modification programs ... This is okay with me since making a transition from 60% carb to 40 to 50% to say 20% is a very good thing - but it takes time ... To the extent carbs are reduced (from 60%) and fats do not exceed 30% (and a lower percentage is advocated by the FDA), only ...
  http://www.thenutritiondebate.com/2014/06/

(1/3362) Epstein-barr virus regulates c-MYC, apoptosis, and tumorigenicity in Burkitt lymphoma.

Loss of the Epstein-Barr virus (EBV) genome from Akata Burkitt lymphoma (BL) cells is coincident with a loss of malignant phenotype, despite the fact that Akata and other EBV-positive BL cells express a restricted set of EBV gene products (type I latency) that are not known to overtly affect cell growth. Here we demonstrate that reestablishment of type I latency in EBV-negative Akata cells restores tumorigenicity and that tumorigenic potential correlates with an increased resistance to apoptosis under growth-limiting conditions. The antiapoptotic effect of EBV was associated with a higher level of Bcl-2 expression and an EBV-dependent decrease in steady-state levels of c-MYC protein. Although the EBV EBNA-1 protein is expressed in all EBV-associated tumors and is reported to have oncogenic potential, enforced expression of EBNA-1 alone in EBV-negative Akata cells failed to restore tumorigenicity or EBV-dependent down-regulation of c-MYC. These data provide direct evidence that EBV contributes to the tumorigenic potential of Burkitt lymphoma and suggest a novel model whereby a restricted latency program of EBV promotes B-cell survival, and thus virus persistence within an immune host, by selectively targeting the expression of c-MYC.  (+info)

(2/3362) Reactive oxygen intermediate-dependent NF-kappaB activation by interleukin-1beta requires 5-lipoxygenase or NADPH oxidase activity.

We previously reported that the role of reactive oxygen intermediates (ROIs) in NF-kappaB activation by proinflammatory cytokines was cell specific. However, the sources for ROIs in various cell types are yet to be determined and might include 5-lipoxygenase (5-LOX) and NADPH oxidase. 5-LOX and 5-LOX activating protein (FLAP) are coexpressed in lymphoid cells but not in monocytic or epithelial cells. Stimulation of lymphoid cells with interleukin-1beta (IL-1beta) led to ROI production and NF-kappaB activation, which could both be blocked by antioxidants or FLAP inhibitors, confirming that 5-LOX was the source of ROIs and was required for NF-kappaB activation in these cells. IL-1beta stimulation of epithelial cells did not generate any ROIs and NF-kappaB induction was not influenced by 5-LOX inhibitors. However, reintroduction of a functional 5-LOX system in these cells allowed ROI production and 5-LOX-dependent NF-kappaB activation. In monocytic cells, IL-1beta treatment led to a production of ROIs which is independent of the 5-LOX enzyme but requires the NADPH oxidase activity. This pathway involves the Rac1 and Cdc42 GTPases, two enzymes which are not required for NF-kappaB activation by IL-1beta in epithelial cells. In conclusion, three different cell-specific pathways lead to NF-kappaB activation by IL-1beta: a pathway dependent on ROI production by 5-LOX in lymphoid cells, an ROI- and 5-LOX-independent pathway in epithelial cells, and a pathway requiring ROI production by NADPH oxidase in monocytic cells.  (+info)

(3/3362) Human granulocytic ehrlichiosis agent and Ehrlichia chaffeensis reside in different cytoplasmic compartments in HL-60 cells.

The human granulocytic ehrlichiosis (HGE) agent resides and multiplies exclusively in cytoplasmic vacuoles of granulocytes. Double immunofluorescence labeling was used to characterize the nature of the HGE agent replicative inclusions and to compare them with inclusions containing the human monocytic ehrlichia, Ehrlichia chaffeensis, in HL-60 cells. Although both Ehrlichia spp. can coinfect HL-60 cells, they resided in separate inclusions. Inclusions of both Ehrlichia spp. were not labeled with either anti-lysosome-associated membrane protein 1 or anti-CD63. Accumulation of myeloperoxidase-positive granules were seen around HGE agent inclusions but not around E. chaffeensis inclusions. 3-(2, 4-Dinitroanilino)-3'-amino-N-methyldipropylamine and acridine orange were not localized to either inclusion type. Vacuolar-type H+-ATPase was not colocalized with HGE agent inclusions but was weakly colocalized with E. chaffeensis inclusions. E. chaffeensis inclusions were labeled with the transferrin receptor, early endosomal antigen 1, and rab5, but HGE agent inclusions were not. Some HGE agent and E. chaffeensis inclusions colocalized with major histocompatibility complex class I and II antigens. These two inclusions were not labeled for annexins I, II, IV, and VI; alpha-adaptin; clathrin heavy chain; or beta-coatomer protein. Vesicle-associated membrane protein 2 colocalized to both inclusions. The cation-independent mannose 6-phosphate receptor was not colocalized with either inclusion type. Endogenously synthesized sphingomyelin, from C6-NBD-ceramide, was not incorporated into either inclusion type. Brefeldin A did not affect the growth of either Ehrlichia sp. in HL-60 cells. These results suggest that the HGE agent resides in inclusions which are neither early nor late endosomes and does not fuse with lysosomes or Golgi-derived vesicles, while E. chaffeensis resides in an early endosomal compartment which accumulates the transferrin receptor.  (+info)

(4/3362) A photodynamic pathway to apoptosis and necrosis induced by dimethyl tetrahydroxyhelianthrone and hypericin in leukaemic cells: possible relevance to photodynamic therapy.

The mechanism of cell death induction by dimethyl tetrahydroxyhelianthrone (DTHe), a new second-generation photodynamic sensitizer, is analysed in human leukaemic cell lines in comparison with the structurally related hypericin. DTHe has a broad range of light spectrum absorption that enables effective utilization of polychromatic light. Photosensitization of HL-60 cells with low doses of DTHe (0.65 microM DTHe and 7.2 J cm(-2) light energy) induced rapid apoptosis of > or =90% of the cells. At doses > or =2 microM, dying cells assumed morphological necrosis with perinucleolar condensation of chromatin in HL-60 and K-562 cell lines. Although nuclear fragmentation that is characteristic to apoptosis was prevented, DNA digestion to oligonucleosomes proceeded unhindered. Such incomplete apoptosis was more prevalent with the related analogue hypericin throughout most doses of photosensitization. Despite hypericin being a stronger photosensitizer, DTHe exhibited advantageous phototoxic properties to tumour cells, initiating apoptosis at concentrations about threefold lower than hypericin. Photosensitization of the cells induced dissociation of the nuclear envelope, releasing lamins into the cytosol. DTHe also differed from hypericin in effects exerted on the nuclear lamina, causing release of an 86-kDa lamin protein into the cytosol that was unique to DTHe. Within the nucleus, nuclear envelope lamin B underwent covalent polymerization, which did not affect apoptotic nuclear fragmentation at low doses of DTHe. At higher doses, polymerization may have been extensive enough to prevent nuclear collapse. Hut-78, CD4+ cells were resistant to the photodynamically activated apoptotic pathway. Beyond the tolerated levels of photodynamic damage, these cells died exclusively via necrosis. Hut-78 cells overexpress Bcl-X(L) as well as a truncated Bcl-X(L)tr isoform that could contribute to the observed resistance to apoptosis.  (+info)

(5/3362) Heparin-binding epidermal growth factor-like growth factor/diphtheria toxin receptor expression by acute myeloid leukemia cells.

Heparin-binding epidermal growth factor-like growth factor (HB-EGF) is an EGF family member expressed by numerous cell types that binds to EGF receptor 1 (HER-1) or 4 (HER-4) inducing mitogenic and/or chemotactic activities. Membrane-bound HB-EGF retains growth activity and adhesion capabilities and the unique property of being the receptor for diphtheria toxin (DT). The interest in studying HB-EGF in acute leukemia stems from these mitogenic, chemotactic, and receptor functions. We analyzed the expression of HB-EGF in L428, Raji, Jurkat, Karpas 299, L540, 2C8, HL-60, U937, THP-1, ML-3, and K562 cell lines and in primary blasts from 12 acute myeloid leukemia (AML) cases, by reverse-transcriptase polymerase chain reaction (RT-PCR) and Northern blot and by the evaluation of sensitivity to DT. The release of functional HB-EGF was assessed by evaluation of its proliferative effects on the HB-EGF-sensitive Balb/c 3T3 cell line. HB-EGF was expressed by all myeloid and T, but not B (L428, Raji), lymphoid cell lines tested, as well as by the majority (8 of 12) of ex vivo AML blasts. Cell lines (except for the K562 cell line) and AML blasts expressing HB-EGF mRNA underwent apoptotic death following exposure to DT, thus demonstrating the presence of the HB-EGF molecule on their membrane. Leukemic cells also released a fully functional HB-EGF molecule that was mitogenic for the Balb/c 3T3 cell line. Factors relevant to the biology of leukemic growth, such as tumor necrosis factor-alpha (TNF-alpha), 1alpha,25-(OH)2D3, and especially all-trans retinoic acid (ATRA), upregulated HB-EGF mRNA in HL-60 or ML-3 cells. Granulocyte-macrophage colony-stimulating factor (GM-CSF) induced HB-EGF mRNA and acquisition of sensitivity to DT in one previously HB-EGF-negative leukemia case. Moreover, the U937 and Karpas 299 cell lines expressed HER-4 mRNA. This work shows that HB-EGF is a growth factor produced by primary leukemic cells and regulated by ATRA, 1alpha, 25-(OH)2D3, and GM-CSF.  (+info)

(6/3362) Interaction of 5-lipoxygenase with cellular proteins.

5-Lipoxygenase (5LO) plays a pivotal role in cellular leukotriene synthesis. To identify proteins interacting with human 5LO, we used a two-hybrid approach to screen a human lung cDNA library. From a total of 1.5 x 10(7) yeast transformants, nine independent clones representing three different proteins were isolated and found to specifically interact with 5LO. Four 1.7- to 1.8-kb clones represented a 16-kDa protein named coactosin-like protein for its significant homology with coactosin, a protein found to be associated with actin in Dictyostelium discoideum. Coactosin-like protein thus may provide a link between 5LO and the cytoskeleton. Two other yeast clones of 1.5 kb encoded transforming growth factor (TGF) type beta receptor-I-associated protein 1 partial cDNA. TGF type beta receptor-I-associated protein 1 recently has been reported to associate with the activated form of the TGF beta receptor I and may be involved in the TGF beta-induced up-regulation of 5LO expression and activity observed in HL-60 and Mono Mac 6 cells. Finally, three identical 2.1-kb clones contained the partial cDNA of a human protein with high homology to a hypothetical helicase K12H4. 8 from Caenorhabditis elegans and consequently was named DeltaK12H4. 8 homologue. Analysis of the predicted amino acid sequence revealed the presence of a RNase III motif and a double-stranded RNA binding domain, indicative of a protein of nuclear origin. The identification of these 5LO-interacting proteins provides additional approaches to studies of the cellular functions of 5LO.  (+info)

(7/3362) Bcl-2 alters the balance between apoptosis and necrosis, but does not prevent cell death induced by oxidized low density lipoproteins.

Oxidized low density lipoproteins (oxLDL) participate in atherosclerosis plaque formation, rupture, and subsequent thrombosis. Because oxLDL are toxic to cultured cells and Bcl-2 protein prevents apoptosis, the present work aimed to study whether Bcl-2 may counterbalance the toxicity of oxLDL. Two experimental model systems were used in which Bcl-2 levels were modulated: 1) lymphocytes in which the (high) basal level of Bcl-2 was reduced by antisense oligonucleotides; 2) HL60 and HL60/B (transduced by Bcl-2) expressing low and high Bcl-2 levels, respectively. In cells expressing relatively high Bcl-2 levels (lymphocytes and HL60/B), oxLDL induced mainly primary necrosis. In cells expressing low Bcl-2 levels (antisense-treated lymphocytes, HL60 and ECV-304 endothelial cells), the rate of oxLDL-induced apoptosis was higher than that of primary necrosis. OxLDL evoked a sustained calcium rise, which is a common trigger to necrosis and apoptosis since both types of cell death were blocked by the calcium chelator EGTA. Conversely, a sustained calcium influx elicited by the calcium ionophore A23187 induced necrosis in cells expressing high Bcl-2 levels and apoptosis in cells expressing low Bcl-2 levels. This suggests that Bcl-2 acts downstream from the calcium peak and inhibits only the apoptotic pathway, not the necrosis pathway, thus explaining the apparent shift from oxLDL-induced apoptosis toward necrosis when Bcl-2 is overexpressed.  (+info)

(8/3362) Effects of novel RAR- and RXR-selective retinoids on myeloid leukemic proliferation and differentiation in vitro.

Retinoids such as all-trans-retinoic acid (ATRA) and 9-cis-retinoic acid (9-cis-RA) have an important role in many aspects of proliferation and differentiation of hematopoietic cells. They exert their effects by binding to retinoic acid receptors (RARs) and/or retinoid X receptors (RXRs). We studied the effects of novel retinoids on proliferation and differentiation of HL-60 and NB4 myeloid leukemic cells, as well as acute promyelocytic leukemia (APL) cells from patients. RXR-selective SR11345 (Retinoid C) had little ability to inhibit the clonal growth and to induce the differentiation of either HL-60 or NB4 cells. However, SR11276 (Retinoid E), which activated both the RAR and RXR classes, and SR11278 (Retinoid D), which activated the RAR subtypes alpha, beta, and gamma, could inhibit clonal growth of both cell types, as well as leukemic cells from APL patients. The combination of ATRA and either SR11276 or SR11278 additively inhibited APL cell proliferation. SR11302 (Retinoid A), with reported anti-AP-1 activity and no activation of RARs and RXR and SR11363 (Retinoid B), which selectively activated RARbeta and gamma, were inactive. The clonal proliferation of both HL-60 and NB4 cells that were pulse-exposed to 10(-9) mol/L ATRA, SR11276, SR11278, or SR11345 for 3 days, washed, and plated in methylcellulose culture were inhibited by 0%, 51%, 21%, and 1% for HL-60 cells and 43%, 41%, 35%, and 1% for NB4, respectively, compared with nontreated control cells. When the HL-60 cells were pulse-exposed to 10(-9) mol/L of either SR11278 or SR11276, plus 10(-9) mol/L ATRA for 3 days, colony numbers were reduced by 46% and 64%, respectively. Induction of leukemic cell differentiation as determined by the nitroblue tetrazolium (NBT) assay showed that the combination of 10(-7) mol/L of either SR11278 or SR11276 with 10(-7) mol/L ATRA had additive effects on HL-60 cells, NB4 cells, and fresh APL cells. Induction of CD11b expression on both HL-60 and NB4 cells occurs during their differentiation. Expression of this antigen was synergistically augmented by the combination of either 10(-7) to 10(-8) mol/L SR11278 or 10(-7) to 10(-9) mol/L SR11276 with 10(-9) mol/L ATRA compared with either analog alone in HL-60 cells. Expression of the novel myeloid specific transcription factor C/EBPepsilon was increased by SR11278 and SR11276 in both the HL-60 and NB4 cell lines. We conclude that retinoids or combination of retinoids with specificities for both RAR and RXR may markedly enhance the ability of ATRA to inhibit clonal growth and induce differentiation of HL-60 and NB4 leukemic cells. This occurs in the absence of continuous contact with retinoids.  (+info)



  • granulocytes
  • Treated cells cease to proliferate, acquire the ability to reduce Nitro Blue Tetrazolium dye, and undergo morphological changes typical of differentiated granulocytes. (biochemj.org)
  • Accordingly, the human leukocyte cell line, HL-60 promyelocytes (which do not respond to FMLP), was purposely differentiated to granulocytes (which do respond to FMLP) and used to partially purify and clone a gene that when transfected into FMLP-unresponsive cells bestowed responsiveness to this and other N-formyl oligopeptides. (wikipedia.org)
  • protein
  • Treatment of the cells with 1,25(OH) 2 D 3 led to a decrease in PP1-like activity in the cytosol fraction, with a concomitant increase in the membrane and nuclear PP1-like activity, as determined when protein phosphatase activity was assayed using myosin light chain as substrate in the presence of 5 n m okadaic acid. (aacrjournals.org)
  • In HL-60/ADR cells (but not in HL-60 cells), the levels of mRNA, protein, and activity in glucosylceramide synthase (GCS), which converts ceramide to glucosylceramide, were up-regulated in response to DOX. (aacrjournals.org)
  • Electrotransfer studies indicate that Ins(1,4,[32P]5)P3 binds specifically to a 260 kDa protein of HL-60 cell membranes. (biochemj.org)
  • This Ins(1,4,5)P3-binding protein selectively binds Ca(2+)-mobilizing inositol phosphates and other inositol phosphates which also bind to the purified InsP3 receptor, suggesting that the Ins(1,4,5)P3-binding protein of HL-60 cell membranes is the InsP3 receptor. (biochemj.org)
  • The results suggest that there is an absolute increase in the level of the InsP3 receptor during HL-60 cell differentiation and that the expression of this signal-transducing protein may be specifically regulated by differentiation factors. (biochemj.org)
  • N-formyl peptide receptor 2 (FPR2) is a G-protein coupled receptor (GPCR) located on the surface of many cell types of various animal species. (wikipedia.org)
  • The human receptor protein is encoded by the FPR2 gene and is activated to regulate cell function by binding any one of a wide variety of ligands including not only certain N-Formylmethionine-containing oligopeptides such as N-Formylmethionine-leucyl-phenylalanine (FMLP) but also the polyunsaturated fatty acid metabolite of arachidonic acid, lipoxin A4 (LXA4). (wikipedia.org)
  • RHO family interacting cell polarization regulator 2 is a protein that in humans is encoded by the RIPOR2 gene. (wikipedia.org)
  • assay
  • The expression of Bcl-2 and Bax proteins in HL-60 cells were visualized by means of immunohistochemical assay and cell viability was determined upon treatment with DEVD-CHO and LA. Typical morphological changes including cell shrinkage, chromatin condensation and characteristic DNA ladder formation in agarose gel electrophoresis were observed. (aacrjournals.org)
  • Furthermore
  • Furthermore, HL-60 cells were xenografted into nude mice and treated by crocin, the tumor weight and size were calculated, and the expression of Bcl-2 and Bax in xenografts was detected by immunohistochemical staining. (hindawi.com)
  • Furthermore, these cells have been used in order to investigate whether intracellular calcium plays a role in caspase activation induced by reactive oxygen species. (wikipedia.org)
  • Furthermore, it was found that CB causes the disorganization of the 50Å microfilaments of mouse epithelial cells which causes the cells to lose their shape. (wikipedia.org)

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  • thymidine
  • The sensitivity to Me 2 SO of HL-60 cells synchronized by double thymidine block was examined and was found to be similar to that of nonsynchronized cells. (aacrjournals.org)
  • D(3)-induced CD11b expression occurred at a similar rate even in G1 cells that were held at the G1/S boundary by thymidine. (biomedsearch.com)
  • induction
  • Our results demonstrate that growth arrest and the induction of differentiation by Sch 52900 is due to the induction of the cell cycle inhibitor p21(WAF) and an inhibition of the extracellular signal-regulated kinase (ERK) signaling pathway which leads to the activation of the transcription factor AP-1. (lu.se)
  • The data are consistent with a stochastic model of induction to differentiation without having any linkage to the cell cycle. (aacrjournals.org)
  • tumor
  • In addition, crocin (6.25, 25 mg/kg) inhibited the tumor weight and size of HL-60 xenografts in nude mice, inhibited Bcl-2 expression, and increased Bax expression in xenografts. (hindawi.com)
  • Signal
  • The first 27 amino acids may encode a signal that allows beta toxin to cross the cell membrane, further evidenced by the presence of beta toxin in extracellular fluid of C. perfringens cultures. (wikipedia.org)
  • leukemic
  • These functions lead to the potential of the microbial metabolite acting as an anticancer agent, specifically for blood cancers, as it has proved to be more effective with leukemic cell lines. (wikipedia.org)
  • cultures
  • Following D(3) treatment, the G1-enriched small cells expressed CD11b slightly faster than unsynchronized cultures or fractions dominated by late G1 cells and/or S phase cells. (biomedsearch.com)
  • regulation
  • siRNAs have been linked through some members to the regulation of cancer cell growth, specifically in prostate adenocarcinoma. (wikipedia.org)
  • inhibits
  • Another group found that CB inhibits the ability of HeLa cells to undergo cytokinesis by decomposition of the contractile ring. (wikipedia.org)
  • In A549 cells, where cytotrienin A has been shown to be less effective, cyt A inhibits the expression of ICAM-1. (wikipedia.org)
  • levels
  • It is also characterized by a low number of platelets, a low number of white blood cells, and elevated serum transaminase levels in the majority of infected patients. (wikipedia.org)
  • results
  • These results indicate that chloroform and trichloroethylene may stimulate H2O2 production in HL-60 cells sensitized by pretreatment of RA. (ehesp.fr)