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Neuroblastoma cell death is induced by inorganic arsenic trioxide (As(2)O(3)) and inhibited by a normal human bone marrow cell-derived factor.

Gesundheit B, Malach L, Or R, Hahn T - Cancer Microenviron (2008)

Bottom Line: As(2)O(3) had a strong inhibitory effect on survival of all tested NB cell lines.BMCM augmented cell growth and survival and reversed the inhibitory action of As(2)O(3) in all tested cell lines, but most strongly in N-type cells(.) While As(2)O(3) effectively reduced survival of all tested NB cell lines, BMCM effectively impacted its inhibitory action.Better understanding of micro-environmental regulators affecting human NB tumor cell growth and survival may be seminal to the development of therapeutic strategies and clinically effective agents for this condition.

View Article: PubMed Central - PubMed

Affiliation: Department of Bone Marrow Transplantation, Hadassah University Hospital, Jerusalem, Israel. gesund@hadassah.org.il

ABSTRACT
Three phenotypically distinct cell types are present in human neuroblastomas (NB) and NB cell lines: I-type stem cells, N-type neuroblastic precursors, and S-type Schwannian/melanoblastic precursors. The stimulation of human N-type neuroblastoma cell proliferation by normal human bone marrow monocytic cell conditioned medium (BMCM) has been demonstrated in vitro, a finding consistent with the high frequency of bone marrow (BM) metastases in patients with advanced NB. Inorganic arsenic trioxide (As(2)O(3)), already clinically approved for the treatment of several hematological malignancies, is currently under investigation for NB. Recent studies show that As(2)O(3) induces apoptosis in NB cells. We examined the impact of BMCM on growth and survival of As(2)O(3)-treated NB cell lines, to evaluate the response of cultured NB cell variants to regulatory agents. We studied the effect of BMCM on survival and clonogenic growth of eleven As(2)O(3)-treated NB cell lines grown in sparsely seeded, non-adherent, semi-solid cultures. As(2)O(3) had a strong inhibitory effect on survival of all tested NB cell lines. BMCM augmented cell growth and survival and reversed the inhibitory action of As(2)O(3) in all tested cell lines, but most strongly in N-type cells(.) While As(2)O(3) effectively reduced survival of all tested NB cell lines, BMCM effectively impacted its inhibitory action. Better understanding of micro-environmental regulators affecting human NB tumor cell growth and survival may be seminal to the development of therapeutic strategies and clinically effective agents for this condition.

No MeSH data available.


Related in: MedlinePlus

Dose-dependent inhibition of As2O3-induced cell death by BMCM (at concentrations indicated in the box) in non-adherent cultures of: a Anchorage-dependent N-type cells. b Anchorage-independent I-type cells. c Anchorage-dependent S-type cells. Viability was quantified, using the XTT reagent by colorimetric measurement of mitochondria-mediated tetrazolium salt reduction, resulting in colored formazan compounds. The results (mean ± SD) of triplicate cultures represent absorbance at 450 nm after 5 h incubation with XTT
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Fig1: Dose-dependent inhibition of As2O3-induced cell death by BMCM (at concentrations indicated in the box) in non-adherent cultures of: a Anchorage-dependent N-type cells. b Anchorage-independent I-type cells. c Anchorage-dependent S-type cells. Viability was quantified, using the XTT reagent by colorimetric measurement of mitochondria-mediated tetrazolium salt reduction, resulting in colored formazan compounds. The results (mean ± SD) of triplicate cultures represent absorbance at 450 nm after 5 h incubation with XTT

Mentions: In agreement with recent reports, we observed that in the micro-molar range As2O3 had a concentration-dependent cytotoxic effect on the 11 cell lines representing all three NB cell types. To examine the impact of BMCM on As2O3-induced cell death, non-adherent cultures of three I-type (NUB 6, MC, LAN 5), three S-type (SHEP, SK-N-LO, LS) and five N-type (IMR 32, IMR 5, KELLY, SY5Y, SK-N-SH) NB cell lines were incubated for 24 h with increasing concentrations of both BMCM and As2O3. Viability was strongly reduced in all five of the anchorage-dependent N-type cell lines in non-adherent cultures in the absence of both As2O3 and BMCM. Fig. 1a shows the results of four out of five cell lines (SK-N-SH not shown). Addition of increasing concentrations of BMCM, without As2O3, to the culture medium resulted in significantly increased cell viability. As2O3 at 2.5 μM considerably reduced viability in all five cell lines treated with a low 2.5% concentration of BMCM, while higher BMCM concentrations (5% and 10%) considerably reduced or abrogated this cytotoxic action of As2O3 at 2.5 μM (Fig. 1a). As2O3 at 5 μM, however, was cytotoxic to the same extent regardless of BMCM.Fig. 1


Neuroblastoma cell death is induced by inorganic arsenic trioxide (As(2)O(3)) and inhibited by a normal human bone marrow cell-derived factor.

Gesundheit B, Malach L, Or R, Hahn T - Cancer Microenviron (2008)

Dose-dependent inhibition of As2O3-induced cell death by BMCM (at concentrations indicated in the box) in non-adherent cultures of: a Anchorage-dependent N-type cells. b Anchorage-independent I-type cells. c Anchorage-dependent S-type cells. Viability was quantified, using the XTT reagent by colorimetric measurement of mitochondria-mediated tetrazolium salt reduction, resulting in colored formazan compounds. The results (mean ± SD) of triplicate cultures represent absorbance at 450 nm after 5 h incubation with XTT
© Copyright Policy
Related In: Results  -  Collection

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getmorefigures.php?uid=PMC2654357&req=5

Fig1: Dose-dependent inhibition of As2O3-induced cell death by BMCM (at concentrations indicated in the box) in non-adherent cultures of: a Anchorage-dependent N-type cells. b Anchorage-independent I-type cells. c Anchorage-dependent S-type cells. Viability was quantified, using the XTT reagent by colorimetric measurement of mitochondria-mediated tetrazolium salt reduction, resulting in colored formazan compounds. The results (mean ± SD) of triplicate cultures represent absorbance at 450 nm after 5 h incubation with XTT
Mentions: In agreement with recent reports, we observed that in the micro-molar range As2O3 had a concentration-dependent cytotoxic effect on the 11 cell lines representing all three NB cell types. To examine the impact of BMCM on As2O3-induced cell death, non-adherent cultures of three I-type (NUB 6, MC, LAN 5), three S-type (SHEP, SK-N-LO, LS) and five N-type (IMR 32, IMR 5, KELLY, SY5Y, SK-N-SH) NB cell lines were incubated for 24 h with increasing concentrations of both BMCM and As2O3. Viability was strongly reduced in all five of the anchorage-dependent N-type cell lines in non-adherent cultures in the absence of both As2O3 and BMCM. Fig. 1a shows the results of four out of five cell lines (SK-N-SH not shown). Addition of increasing concentrations of BMCM, without As2O3, to the culture medium resulted in significantly increased cell viability. As2O3 at 2.5 μM considerably reduced viability in all five cell lines treated with a low 2.5% concentration of BMCM, while higher BMCM concentrations (5% and 10%) considerably reduced or abrogated this cytotoxic action of As2O3 at 2.5 μM (Fig. 1a). As2O3 at 5 μM, however, was cytotoxic to the same extent regardless of BMCM.Fig. 1

Bottom Line: As(2)O(3) had a strong inhibitory effect on survival of all tested NB cell lines.BMCM augmented cell growth and survival and reversed the inhibitory action of As(2)O(3) in all tested cell lines, but most strongly in N-type cells(.) While As(2)O(3) effectively reduced survival of all tested NB cell lines, BMCM effectively impacted its inhibitory action.Better understanding of micro-environmental regulators affecting human NB tumor cell growth and survival may be seminal to the development of therapeutic strategies and clinically effective agents for this condition.

View Article: PubMed Central - PubMed

Affiliation: Department of Bone Marrow Transplantation, Hadassah University Hospital, Jerusalem, Israel. gesund@hadassah.org.il

ABSTRACT
Three phenotypically distinct cell types are present in human neuroblastomas (NB) and NB cell lines: I-type stem cells, N-type neuroblastic precursors, and S-type Schwannian/melanoblastic precursors. The stimulation of human N-type neuroblastoma cell proliferation by normal human bone marrow monocytic cell conditioned medium (BMCM) has been demonstrated in vitro, a finding consistent with the high frequency of bone marrow (BM) metastases in patients with advanced NB. Inorganic arsenic trioxide (As(2)O(3)), already clinically approved for the treatment of several hematological malignancies, is currently under investigation for NB. Recent studies show that As(2)O(3) induces apoptosis in NB cells. We examined the impact of BMCM on growth and survival of As(2)O(3)-treated NB cell lines, to evaluate the response of cultured NB cell variants to regulatory agents. We studied the effect of BMCM on survival and clonogenic growth of eleven As(2)O(3)-treated NB cell lines grown in sparsely seeded, non-adherent, semi-solid cultures. As(2)O(3) had a strong inhibitory effect on survival of all tested NB cell lines. BMCM augmented cell growth and survival and reversed the inhibitory action of As(2)O(3) in all tested cell lines, but most strongly in N-type cells(.) While As(2)O(3) effectively reduced survival of all tested NB cell lines, BMCM effectively impacted its inhibitory action. Better understanding of micro-environmental regulators affecting human NB tumor cell growth and survival may be seminal to the development of therapeutic strategies and clinically effective agents for this condition.

No MeSH data available.


Related in: MedlinePlus