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.
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.
Hodge
Greg
G
Haematology/Oncology Department, Women's and Children's Hospital, North Adelaide, Australia.
Davis
Stephen
S
Rice
Michael
M
Tapp
Heather
H
Saxon
Ben
B
Revesz
Tamas
T
Clin Exp Immunol. 2005 Jan;139(1):159-64
15606627
Br J Biomed Sci. 2004;61(2):71-4
15250668
Antimicrob Agents Chemother. 1983 May;23(5):700-2
6870217
J Nutr. 2001 Mar;131(3s):1067S-70S
11238818
J Antimicrob Chemother. 2004 May;53(5):832-6
15044429
Arch Neurol. 2001 Jan;58(1):91-7
11176941
Eur Respir J. 2005 Mar;25(3):447-54
15738287
J Antimicrob Chemother. 2003 Mar;51(3):593-7
12615859
Cytometry. 2002 Aug 1;48(4):209-15
12210145
Mycoses. 2005 Mar;48(2):95-100
15743425
Annu Rev Immunol. 1992;10:411-52
1590993
Br J Haematol. 1993 Mar;83(3):419-27
8485047
Blood. 2003 Dec 15;102(13):4541-6
12920041
Cancer Treat Rev. 2001 Dec;27(6):327-37
11908926
Cytokine. 2000 Dec;12(12):1763-8
11097745
Br J Haematol. 2001 Nov;115(2):376-81
11703339
Mol Pharmacol. 1998 Mar;53(3):402-7
9495804
Blood. 2005 Jul 15;106(2):408-18
15797997
Bone Marrow Transplant. 1994 Jun;13(6):703-4
7920297
J Nutr Sci Vitaminol (Tokyo). 1999 Dec;45(6):785-90
10737231
Jpn J Cancer Res. 2001 Nov;92(11):1157-65
11714439