Recombinant interferon- γ inhibits the growth of IL-6-dependent human multiple myeloma cell lines in vitro

BackgroundAccumulating reports indicate that statins widely prescribed for hypercholesteromia have antineoplastic activity. We hypothesized that because statins inhibit farnesylation of Ras that is often mutated in multiple myeloma (MM), as well as the production of interleukin (IL)-6, a key cytokine in MM, they may have antiproliferative and/or proapoptotic effects in this malignancy.MethodsU266, RPMI 8226, and ARH77 were treated with simvastatin (0-30 μM) for 5 days. The following aspects were evaluated: viability (IC50), cell cycle, cell death, cytoplasmic calcium ion levels, supernatant IL-6 levels, and tyrosine kinase activity.ResultsExposure of all cell lines to simvastatin resulted in reduced viability with IC50s of 4.5 μM for ARH77, 8 μM for RPMI 8226, and 13 μM for U266. The decreased viability is attributed to cell-cycle arrest (U266, G1; RPMI 8226, G2M) and cell death. ARH77 underwent apoptosis, whereas U266 and RPMI 8226 displayed a more necrotic form of death. Cytoplasmic calcium levels decreased significantly in all treated cell lines. IL-6 secretion from U266 cells was abrogated on treatment with simvastatin, whereas total tyrosine phosphorylation was unaffected.ConclusionsSimvastatin displays significant antimyeloma activity in vitro. Further research is warranted for elucidation of the modulated molecular pathways and clinical relevance.

Download Full-text

The effects on growth and survival of IL‐6 can be dissociated in the U‐266‐1970/U‐266‐1984 and HL407E/HL407L human multiple myeloma cell lines

British Journal of Haematology ◽

10.1046/j.1365-2141.1997.1903004.x ◽

1997 ◽

Vol 98 (1) ◽

pp. 126-133 ◽

Cited By ~ 14

Author(s):

Helena Spets ◽

Helena Jernberg‐Wiklund ◽

Clara Sambade ◽

Ola Söderberg ◽

Kenneth Nilsson

Keyword(s):

Multiple Myeloma ◽

Cell Lines ◽

Myeloma Cell ◽

Growth And Survival ◽

Multiple Myeloma Cell ◽

Human Multiple Myeloma

Download Full-text

Cytotoxic Effect of Moringa Oleifera Leaf Extracts On Human Multiple Myeloma Cell Lines

Trends in Medical Research ◽

10.3923/tmr.2007.44.50 ◽

2007 ◽

Vol 2 (1) ◽

pp. 44-50 ◽

Cited By ~ 21

Author(s):

M.V.S. Parvathy . ◽

A. Umamaheshwari .

Keyword(s):

Multiple Myeloma ◽

Cell Lines ◽

Cytotoxic Effect ◽

Moringa Oleifera ◽

Myeloma Cell ◽

Leaf Extracts ◽

Multiple Myeloma Cell ◽

Human Multiple Myeloma

Download Full-text

CD40 activation mediates p53-dependent cell cycle regulation in human multiple myeloma cell lines

Blood ◽

10.1182/blood.v95.3.1039.003k02_1039_1046 ◽

2000 ◽

Vol 95 (3) ◽

pp. 1039-1046 ◽

Cited By ~ 42

Author(s):

G. Teoh ◽

Y.-T. Tai ◽

M. Urashima ◽

S. Shirahama ◽

M. Matsuzaki ◽

...

Keyword(s):

Multiple Myeloma ◽

Cell Lines ◽

Growth Arrest ◽

Myeloma Cell ◽

Luciferase Reporter ◽

Temperature Sensitive ◽

Multiple Myeloma Cell ◽

Cd40 Activation ◽

Human Multiple Myeloma ◽

Rpmi 8226

It has been reported that the activation of multiple myeloma (MM) cells by CD40 induces proliferation, growth arrest, and apoptosis. To determine whether the biologic sequelae of CD40 activation in MM cells depends on p53 function, we identified temperature-sensitive p53 mutations in the RPMI 8226 (tsp53E285K) and the HS Sultan (tsp53Y163H) MM cell lines. These cells were then used as a model system of inducible wtp53-like function because wild-type-like p53 is induced at permissive (30°C) but not at restrictive (37°C) temperatures. Using p21-luciferase reporter assays, we confirmed that CD40 induces p53 transactivation in RPMI 8226 and HS Sultan cells cultured under permissive, but not restrictive, conditions. Furthermore, CD40 activation of these MM cells under permissive, but not restrictive, temperatures increased the expression of p53 and p21 mRNA and protein. Importantly, CD40 activation induced the proliferation of RPMI 8226 and HS Sultan cells at restrictive temperatures and growth arrest and increased subG1 phase cells at permissive temperatures. These data confirmed that CD40 activation might have distinct biologic sequelae in MM cells, depending on their p53 status.

Download Full-text

Fas/APO-1 (CD95)–Mediated Apoptosis Is Activated by Interferon-γ and Interferon- in Interleukin-6 (IL-6)–Dependent and IL-6–Independent Multiple Myeloma Cell Lines

Blood ◽

10.1182/blood.v92.8.2914 ◽

1998 ◽

Vol 92 (8) ◽

pp. 2914-2923 ◽

Cited By ~ 54

Author(s):

Helena Spets ◽

Patrik Georgii-Hemming ◽

Jan Siljason ◽

Kenneth Nilsson ◽

Helena Jernberg-Wiklund

Keyword(s):

Multiple Myeloma ◽

Cell Lines ◽

Poor Response ◽

Antigen Expression ◽

Myeloma Cell ◽

Interferon Γ ◽

Dependent Manner ◽

Multiple Myeloma Cell ◽

Ifn Γ ◽

Induced Apoptosis

Abstract A poor response to Fas-induced apoptosis is evident in some multiple myeloma (MM) cell lines and primary cells. In this study, we have examined the possibility to increase the sensitivity to Fas-induced apoptosis by pretreatment of MM cells with interferon-γ (IFN-γ) or interferon- (IFN-). Both IFN-γ and IFN- markedly increased the Fas-induced apoptosis in all cell lines tested (U-266-1970, U-266-1984, and U-1958). In the U-266-1970 and U-1958 cell lines, pretreatment with either IFN-γ or IFN- also inhibited proliferation in a dose-dependent manner. In contrast, IFN-γ activation of the Fas death pathway in the U-266-1984 cells was not accompanied by growth inhibition. Incubation with the IFNs increased the Fas antigen expression in one of three cell lines but did not alter the expression of Bcl-2 or Bax. The IFNs are important regulators of growth and survival in MM cells. Our results suggest that activation of Fas-mediated apoptosis is a novel mechanism by which the IFNs exert inhibitory effects on MM cells. © 1998 by The American Society of Hematology.

Download Full-text

Abstract 124: Involvement of the notch pathway in the clonogenicity of human multiple myeloma cell lines

10.1158/1538-7445.am10-124 ◽

2010 ◽

Author(s):

David Chiron ◽

Martine Amiot ◽

Jerome Moreaux ◽

Bernard Klein ◽

Catherine Pellat-Deceunynck

Keyword(s):

Multiple Myeloma ◽

Cell Lines ◽

Notch Pathway ◽

Myeloma Cell ◽

Multiple Myeloma Cell ◽

Human Multiple Myeloma

Download Full-text

The hematopoietic transcription factor PU.1 is downregulated in human multiple myeloma cell lines

Blood ◽

10.1182/blood.v86.7.2747.2747 ◽

1995 ◽

Vol 86 (7) ◽

pp. 2747-2753 ◽

Cited By ~ 20

Author(s):

M Pettersson ◽

C Sundstrom ◽

K Nilsson ◽

LG Larsson

Keyword(s):

Multiple Myeloma ◽

B Cells ◽

B Cell ◽

Cell Lines ◽

Myeloma Cell ◽

Binding Activity ◽

Multiple Myeloma Cell ◽

Dna Binding Activity ◽

Human Multiple Myeloma ◽

Expression And Activity

Abstract PU.1 is a hematopoietic transcription factor belonging to the Ets-family. It is identical to the Spi-1 oncogene, which is implicated in spleen focus-forming virus-induced murine erythroleukemias. PU.1 seems to be required for early development of multiple hematopoietic lineages, but its expression in mature cells is preferentially observed in cells of the B-cell-and monocyte/macrophage-differentiation lineage. It binds the so-called Pu box, an important tissue-specific regulatory DNA element present in a number of genes expressed in these cell lineages. We have analyzed the expression and activity of PU.1 during human B-cell development using a panel of B-cell lines representing different stages of maturation, from early precursors to differentiated plasma cells. PU.1 mRNA expression and PU.1 DNA binding activity, as measured by Northern blot analysis and electrophoretic mobility shift assay, respectively, were evident in cell lines representing pro-B, pre- B, and mature B cells. We could also show Pu box-dependent transactivation of a reporter gene in transient transfections in these cell lines. In contrast, in a number of multiple myeloma cell lines, representing differentiated, plasma cell-like B cells, PU.1 DNA binding activity, mRNA expression, and Pu box-dependent transactivation were absent or detectable at a very low level. In lymphoblastoid cell lines, which exemplify an intermediate stage of B-cell differentiation, a reduced expression and activity were observed. The findings in the human multiple myeloma cell lines represent the first examples of B cells with downregulated PU.1 expression and apparently contradict observations in the murine system in which PU.1 is expressed and active in plasmacytoma cell lines. At present, it is unclear whether the lack of PU.1 expression and activity in human multiple myeloma cell lines represents a malignancy-associated defect in these cells or exemplifies a normal developmental regulation in terminally differentiated B cells.

Download Full-text