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Garlic compounds selectively kill childhood pre-B acute lymphoblastic leukemia cells in vitro without reducing T-cell function: Potential therapeutic use in the treatment of ALL.

Hodge G, Davis S, Rice M, Tapp H, Saxon B, Revesz T - Biologics (2008)

Bottom Line: At concentrations of garlic compounds that did not result in significant increases in Annexin V and 7-AAD staining of normal lymphocytes, there was a significant increase in apoptosis of ALL cells with no alteration of T-cell proliferation as determined by CD25/CD69 upregulation or interferongamma, interleukin-2 or tumor necrosis factor-alpha intracellular cytokine production.In contrast, the presence of chemotherapeutic agents resulted in nonselective increases in both lymphocyte and ALL apoptosis and a decrease in T-cell proliferation and cytokine production.In conclusion, we show selective apoptosis of malignant cells by garlic compounds that do not alter T-cell immune function and indicate the potential therapeutic benefit of garlic compounds in the treatment of childhood ALL.

View Article: PubMed Central - PubMed

Affiliation: Haematology/Oncology Department, Women's and Children's Hospital, North Adelaide, Australia.

ABSTRACT
Drugs used for remission induction therapy for childhood precursor-B acute lymphoblastic leukemia (ALL) are nonselective for malignant cells. Several garlic compounds have been shown to induce apoptosis of cancer cells and to alter lymphocyte function. To investigate the effect of garlic on the apoptosis of ALL cells and lymphocyte immune function, cells from newly diagnosed childhood ALL patients were cultured with several commonly used chemotherapeutic agents and several garlic compounds. Apoptosis, lymphocyte proliferation and T-cell cytokine production were determined using multiparameter flow cytometry. At concentrations of garlic compounds that did not result in significant increases in Annexin V and 7-AAD staining of normal lymphocytes, there was a significant increase in apoptosis of ALL cells with no alteration of T-cell proliferation as determined by CD25/CD69 upregulation or interferongamma, interleukin-2 or tumor necrosis factor-alpha intracellular cytokine production. In contrast, the presence of chemotherapeutic agents resulted in nonselective increases in both lymphocyte and ALL apoptosis and a decrease in T-cell proliferation and cytokine production. In conclusion, we show selective apoptosis of malignant cells by garlic compounds that do not alter T-cell immune function and indicate the potential therapeutic benefit of garlic compounds in the treatment of childhood ALL.

No MeSH data available.


Related in: MedlinePlus

Graph showing dose-dependent inhibition of T-cell IFNγ production in the presence of increasing concentrations of D: daunorubicin (0.002, 0.02, 0.2, 2.0, 20 μg/mL), V: vincritine (0.005, 0.05, 0.5, 5, 50 μg/mL), Al: allitridium (0.0002, 0.005, 0.02, 0.2, 2.5 μg/mL), L: L-asparaginase (0.003, 0.03, 0.3, 3, 10 μg/mL), Aj: ajoene (0.0005, 0.005, 0.01, 0.5, 5 μg/mL), G: garlic extract (0.001, 0.01, 0.1, 1, 10 μg/mL) and P: Prednisolone (0.08, 0.8, 8, 80, 250 μg/mL).
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f3-btt-2-143: Graph showing dose-dependent inhibition of T-cell IFNγ production in the presence of increasing concentrations of D: daunorubicin (0.002, 0.02, 0.2, 2.0, 20 μg/mL), V: vincritine (0.005, 0.05, 0.5, 5, 50 μg/mL), Al: allitridium (0.0002, 0.005, 0.02, 0.2, 2.5 μg/mL), L: L-asparaginase (0.003, 0.03, 0.3, 3, 10 μg/mL), Aj: ajoene (0.0005, 0.005, 0.01, 0.5, 5 μg/mL), G: garlic extract (0.001, 0.01, 0.1, 1, 10 μg/mL) and P: Prednisolone (0.08, 0.8, 8, 80, 250 μg/mL).

Mentions: At concentrations of garlic compounds that resulted in significant apoptosis of ALL cells but not of T-cells as determined by Annexin V and 7-AAD staining, there was no significant change in intracellular interferonγ (IFNγ), interleukin-2 (IL-2), or tumor necrosis factor-α (TNFα) production (Table 3). In the presence of most drugs, there was a dose-dependent inhibition in intracellular IFNγ, IL-2, TNFα production (p < 0.05). The dose-dependent inhibition of IFNγ by drugs is shown in Figure 3 (dose-dependent data for IL-2 and TNFα not shown). The inhibition of these cytokines was significantly greater in the presence of most drugs compared with garlic compounds. Representative dot plots showing intracellular CD8+ and CD8− (CD4+) T-cell production of IFNγ, IL-2 and TNFα in the presence of 0.1 μg/mL garlic extract and 50 μg/mL vincristine from PBMC from a patient with ALL compared with an aged-matched control with no drugs is shown in Figure 4. The percentage and mean fluorescence intensity of CD8+ and CD8− (CD4+) T-cells producing IFNγ, IL-2, and TNFα was significantly inhibited (p < 0.05) in the presence of vincristine but not garlic extract (p < 0.05) compared with control without drugs (data not shown). Intracellular CD8+ and CD8− (CD4+) T-cell production of IFNγ, IL-2, and TNFα by PBMC from the ALL patient was significantly decreased (p < 0.05) compared with the healthy age-matched control.


Garlic compounds selectively kill childhood pre-B acute lymphoblastic leukemia cells in vitro without reducing T-cell function: Potential therapeutic use in the treatment of ALL.

Hodge G, Davis S, Rice M, Tapp H, Saxon B, Revesz T - Biologics (2008)

Graph showing dose-dependent inhibition of T-cell IFNγ production in the presence of increasing concentrations of D: daunorubicin (0.002, 0.02, 0.2, 2.0, 20 μg/mL), V: vincritine (0.005, 0.05, 0.5, 5, 50 μg/mL), Al: allitridium (0.0002, 0.005, 0.02, 0.2, 2.5 μg/mL), L: L-asparaginase (0.003, 0.03, 0.3, 3, 10 μg/mL), Aj: ajoene (0.0005, 0.005, 0.01, 0.5, 5 μg/mL), G: garlic extract (0.001, 0.01, 0.1, 1, 10 μg/mL) and P: Prednisolone (0.08, 0.8, 8, 80, 250 μg/mL).
© Copyright Policy
Related In: Results  -  Collection

Show All Figures
getmorefigures.php?uid=PMC2727784&req=5

f3-btt-2-143: Graph showing dose-dependent inhibition of T-cell IFNγ production in the presence of increasing concentrations of D: daunorubicin (0.002, 0.02, 0.2, 2.0, 20 μg/mL), V: vincritine (0.005, 0.05, 0.5, 5, 50 μg/mL), Al: allitridium (0.0002, 0.005, 0.02, 0.2, 2.5 μg/mL), L: L-asparaginase (0.003, 0.03, 0.3, 3, 10 μg/mL), Aj: ajoene (0.0005, 0.005, 0.01, 0.5, 5 μg/mL), G: garlic extract (0.001, 0.01, 0.1, 1, 10 μg/mL) and P: Prednisolone (0.08, 0.8, 8, 80, 250 μg/mL).
Mentions: At concentrations of garlic compounds that resulted in significant apoptosis of ALL cells but not of T-cells as determined by Annexin V and 7-AAD staining, there was no significant change in intracellular interferonγ (IFNγ), interleukin-2 (IL-2), or tumor necrosis factor-α (TNFα) production (Table 3). In the presence of most drugs, there was a dose-dependent inhibition in intracellular IFNγ, IL-2, TNFα production (p < 0.05). The dose-dependent inhibition of IFNγ by drugs is shown in Figure 3 (dose-dependent data for IL-2 and TNFα not shown). The inhibition of these cytokines was significantly greater in the presence of most drugs compared with garlic compounds. Representative dot plots showing intracellular CD8+ and CD8− (CD4+) T-cell production of IFNγ, IL-2 and TNFα in the presence of 0.1 μg/mL garlic extract and 50 μg/mL vincristine from PBMC from a patient with ALL compared with an aged-matched control with no drugs is shown in Figure 4. The percentage and mean fluorescence intensity of CD8+ and CD8− (CD4+) T-cells producing IFNγ, IL-2, and TNFα was significantly inhibited (p < 0.05) in the presence of vincristine but not garlic extract (p < 0.05) compared with control without drugs (data not shown). Intracellular CD8+ and CD8− (CD4+) T-cell production of IFNγ, IL-2, and TNFα by PBMC from the ALL patient was significantly decreased (p < 0.05) compared with the healthy age-matched control.

Bottom Line: At concentrations of garlic compounds that did not result in significant increases in Annexin V and 7-AAD staining of normal lymphocytes, there was a significant increase in apoptosis of ALL cells with no alteration of T-cell proliferation as determined by CD25/CD69 upregulation or interferongamma, interleukin-2 or tumor necrosis factor-alpha intracellular cytokine production.In contrast, the presence of chemotherapeutic agents resulted in nonselective increases in both lymphocyte and ALL apoptosis and a decrease in T-cell proliferation and cytokine production.In conclusion, we show selective apoptosis of malignant cells by garlic compounds that do not alter T-cell immune function and indicate the potential therapeutic benefit of garlic compounds in the treatment of childhood ALL.

View Article: PubMed Central - PubMed

Affiliation: Haematology/Oncology Department, Women's and Children's Hospital, North Adelaide, Australia.

ABSTRACT
Drugs used for remission induction therapy for childhood precursor-B acute lymphoblastic leukemia (ALL) are nonselective for malignant cells. Several garlic compounds have been shown to induce apoptosis of cancer cells and to alter lymphocyte function. To investigate the effect of garlic on the apoptosis of ALL cells and lymphocyte immune function, cells from newly diagnosed childhood ALL patients were cultured with several commonly used chemotherapeutic agents and several garlic compounds. Apoptosis, lymphocyte proliferation and T-cell cytokine production were determined using multiparameter flow cytometry. At concentrations of garlic compounds that did not result in significant increases in Annexin V and 7-AAD staining of normal lymphocytes, there was a significant increase in apoptosis of ALL cells with no alteration of T-cell proliferation as determined by CD25/CD69 upregulation or interferongamma, interleukin-2 or tumor necrosis factor-alpha intracellular cytokine production. In contrast, the presence of chemotherapeutic agents resulted in nonselective increases in both lymphocyte and ALL apoptosis and a decrease in T-cell proliferation and cytokine production. In conclusion, we show selective apoptosis of malignant cells by garlic compounds that do not alter T-cell immune function and indicate the potential therapeutic benefit of garlic compounds in the treatment of childhood ALL.

No MeSH data available.


Related in: MedlinePlus