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Allium compounds, dipropyl and dimethyl thiosulfinates as antiproliferative and differentiating agents of human acute myeloid leukemia cell lines.

Merhi F, Auger J, Rendu F, Bauvois B - Biologics (2008)

Bottom Line: The beneficial effects appear related to the organosulfur products generated upon processing of Allium.Leukemia cells from patients with acute myeloid leukemia (AML) display high proliferative capacity and have a reduced capacity of undergoing apoptosis and maturation.By establishing for the first time that Pr(2)TS and Me(2)TS affect proliferation, differentiation and secretion of leukemic cell lines, this study provides the opportunity to explore the potential efficiency of these molecules in AML.

View Article: PubMed Central - PubMed

Affiliation: UMR 7131 UPMC Paris Universitas/ CNRS, Groupe Hospitalier Broussais-HEGP, Paris, France.

ABSTRACT
Epidemiologic studies support the premise that Allium vegetables may lower the risk of cancers. The beneficial effects appear related to the organosulfur products generated upon processing of Allium. Leukemia cells from patients with acute myeloid leukemia (AML) display high proliferative capacity and have a reduced capacity of undergoing apoptosis and maturation. Whether the sulfur-containing molecules thiosulfinates (TS), diallyl TS (All(2)TS), dipropyl TS (Pr(2)TS) and dimethyl TS (Me(2)TS), are able to exert chemopreventative activity against AML is presently unknown. The present study was an evaluation of proliferation, cytotoxicity, differentiation and secretion of AML cell lines (U937, NB4, HL-60, MonoMac-6) in response to treatment with these TS and their related sulfides (diallylsulfide, diallyl disulfide, dipropyl disulfide, dimethyl disulfide). As assessed by flow cytometry, ELISA, gelatin zymogaphy and RT-PCR, we showed that Pr(2)TS and Me(2)TS, but not All(2)TS and sulfides, 1) inhibited cell proliferation in dose- and time-dependent manner and this process was neither due to cytotoxicity nor apoptosis, 2) induced macrophage maturation, and 3) inhibited the levels of secreted MMP-9 (protein and activity) and TNF-alpha protein, without altering mRNA levels. By establishing for the first time that Pr(2)TS and Me(2)TS affect proliferation, differentiation and secretion of leukemic cell lines, this study provides the opportunity to explore the potential efficiency of these molecules in AML.

No MeSH data available.


Related in: MedlinePlus

Effects of Pr2TS and Me2TS on VEGF and TNF-α expression in PMA-activated U937 and NB4 cells. U937 and NB4 cells (105/mL) activated with 1 ng/mL PMA, were cultured for 24 or 72 h in the absence or presence of Pr2TS and Me2TS (5μM). (A) ELISA analyses of VEGF and TNF-α concentrations in culture media of 72 h-treated cells. Values are expressed as pg/mL/105 cells. (B) RT-PCR analysis of VEGF, TNF-α and β2-microglobulin transcripts in 24 h-treated cells.
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f7-btt-2-885: Effects of Pr2TS and Me2TS on VEGF and TNF-α expression in PMA-activated U937 and NB4 cells. U937 and NB4 cells (105/mL) activated with 1 ng/mL PMA, were cultured for 24 or 72 h in the absence or presence of Pr2TS and Me2TS (5μM). (A) ELISA analyses of VEGF and TNF-α concentrations in culture media of 72 h-treated cells. Values are expressed as pg/mL/105 cells. (B) RT-PCR analysis of VEGF, TNF-α and β2-microglobulin transcripts in 24 h-treated cells.

Mentions: As assessed by ELISA and zymography analyses of the conditioned media from day 3-cultured cells, very low amounts of matrix metalloproteinase-9 (MMP-9, 92 kDa) were produced by U937 cells and NB4 cells (<10 ng/mL). In parallel, no change in MMP-9 mRNA expression was observed to Pr2TS or Me2TS (from 24 to 72 h, data not shown). As described previously (Watanabe et al 1993), exposure to PMA markedly increased the levels of released MMP-9 as assessed by its gelatinolytic activity (about 10-fold increase, Figure 6A). Addition of Pr2TS or Me2TS (5 μM) to the culture medium resulted in a reduction of released MMP-9 activity from PMA-activated cells (Figure 6A). ELISA data confirmed that diminished MMP-9 gelatinolytic activity resulted from the decrease in MMP-9 protein (Figure 6B). PCR analysis was used to examine the steady-state MMP-9 mRNA alteration before and after Pr2TS or Me2TS treatment. As shown in Figure 6C, Pr2TS or Me2TS did not alter the apparent levels of MMP-9 transcripts in PMA-activated cells treated for 24 h. In parallel, the amounts of TNF-α protein released from PMA-activated cells were also strongly diminished following Pr2TS or Me2TS treatment (Figure 7A) while the mRNA contents of TNF-α were slightly affected by Pr2TS or Me2TS at 24 h (Figure 7B), TNF-α mRNA/β2 mRNA ratios being decreased by 25% for Pr2TS and 49% for Me2TS. In both cell types, vascular endothelial growth factor (VEGF) protein and mRNA levels remained almost unchanged by Pr2TS and Me2TS (Figure 7A and B).


Allium compounds, dipropyl and dimethyl thiosulfinates as antiproliferative and differentiating agents of human acute myeloid leukemia cell lines.

Merhi F, Auger J, Rendu F, Bauvois B - Biologics (2008)

Effects of Pr2TS and Me2TS on VEGF and TNF-α expression in PMA-activated U937 and NB4 cells. U937 and NB4 cells (105/mL) activated with 1 ng/mL PMA, were cultured for 24 or 72 h in the absence or presence of Pr2TS and Me2TS (5μM). (A) ELISA analyses of VEGF and TNF-α concentrations in culture media of 72 h-treated cells. Values are expressed as pg/mL/105 cells. (B) RT-PCR analysis of VEGF, TNF-α and β2-microglobulin transcripts in 24 h-treated cells.
© Copyright Policy
Related In: Results  -  Collection

Show All Figures
getmorefigures.php?uid=PMC2727902&req=5

f7-btt-2-885: Effects of Pr2TS and Me2TS on VEGF and TNF-α expression in PMA-activated U937 and NB4 cells. U937 and NB4 cells (105/mL) activated with 1 ng/mL PMA, were cultured for 24 or 72 h in the absence or presence of Pr2TS and Me2TS (5μM). (A) ELISA analyses of VEGF and TNF-α concentrations in culture media of 72 h-treated cells. Values are expressed as pg/mL/105 cells. (B) RT-PCR analysis of VEGF, TNF-α and β2-microglobulin transcripts in 24 h-treated cells.
Mentions: As assessed by ELISA and zymography analyses of the conditioned media from day 3-cultured cells, very low amounts of matrix metalloproteinase-9 (MMP-9, 92 kDa) were produced by U937 cells and NB4 cells (<10 ng/mL). In parallel, no change in MMP-9 mRNA expression was observed to Pr2TS or Me2TS (from 24 to 72 h, data not shown). As described previously (Watanabe et al 1993), exposure to PMA markedly increased the levels of released MMP-9 as assessed by its gelatinolytic activity (about 10-fold increase, Figure 6A). Addition of Pr2TS or Me2TS (5 μM) to the culture medium resulted in a reduction of released MMP-9 activity from PMA-activated cells (Figure 6A). ELISA data confirmed that diminished MMP-9 gelatinolytic activity resulted from the decrease in MMP-9 protein (Figure 6B). PCR analysis was used to examine the steady-state MMP-9 mRNA alteration before and after Pr2TS or Me2TS treatment. As shown in Figure 6C, Pr2TS or Me2TS did not alter the apparent levels of MMP-9 transcripts in PMA-activated cells treated for 24 h. In parallel, the amounts of TNF-α protein released from PMA-activated cells were also strongly diminished following Pr2TS or Me2TS treatment (Figure 7A) while the mRNA contents of TNF-α were slightly affected by Pr2TS or Me2TS at 24 h (Figure 7B), TNF-α mRNA/β2 mRNA ratios being decreased by 25% for Pr2TS and 49% for Me2TS. In both cell types, vascular endothelial growth factor (VEGF) protein and mRNA levels remained almost unchanged by Pr2TS and Me2TS (Figure 7A and B).

Bottom Line: The beneficial effects appear related to the organosulfur products generated upon processing of Allium.Leukemia cells from patients with acute myeloid leukemia (AML) display high proliferative capacity and have a reduced capacity of undergoing apoptosis and maturation.By establishing for the first time that Pr(2)TS and Me(2)TS affect proliferation, differentiation and secretion of leukemic cell lines, this study provides the opportunity to explore the potential efficiency of these molecules in AML.

View Article: PubMed Central - PubMed

Affiliation: UMR 7131 UPMC Paris Universitas/ CNRS, Groupe Hospitalier Broussais-HEGP, Paris, France.

ABSTRACT
Epidemiologic studies support the premise that Allium vegetables may lower the risk of cancers. The beneficial effects appear related to the organosulfur products generated upon processing of Allium. Leukemia cells from patients with acute myeloid leukemia (AML) display high proliferative capacity and have a reduced capacity of undergoing apoptosis and maturation. Whether the sulfur-containing molecules thiosulfinates (TS), diallyl TS (All(2)TS), dipropyl TS (Pr(2)TS) and dimethyl TS (Me(2)TS), are able to exert chemopreventative activity against AML is presently unknown. The present study was an evaluation of proliferation, cytotoxicity, differentiation and secretion of AML cell lines (U937, NB4, HL-60, MonoMac-6) in response to treatment with these TS and their related sulfides (diallylsulfide, diallyl disulfide, dipropyl disulfide, dimethyl disulfide). As assessed by flow cytometry, ELISA, gelatin zymogaphy and RT-PCR, we showed that Pr(2)TS and Me(2)TS, but not All(2)TS and sulfides, 1) inhibited cell proliferation in dose- and time-dependent manner and this process was neither due to cytotoxicity nor apoptosis, 2) induced macrophage maturation, and 3) inhibited the levels of secreted MMP-9 (protein and activity) and TNF-alpha protein, without altering mRNA levels. By establishing for the first time that Pr(2)TS and Me(2)TS affect proliferation, differentiation and secretion of leukemic cell lines, this study provides the opportunity to explore the potential efficiency of these molecules in AML.

No MeSH data available.


Related in: MedlinePlus