Allicin stimulates lymphocytes and elicits an antitumor effect: a possible role of p21ras.
Allicin, the main organic allyl sulfur component in garlic, exhibits immune-stimulatory and antitumor properties. Allicin stimulated [(3)H]thymidine incorporation in mouse splenocytes and enhanced cell-mediated cytotoxicity in human peripheral mononuclear cells. Multiple administration (i.p.) of allicin elicited a marked antitumor effect in mice inoculated with B-16 melanoma and MCA-105 fibrosarcoma. The immune-stimulatory and antitumor effects of allicin are characterized by a bell-shaped curve, i.e. allicin at high, supra-optimal concentrations is less effective or inhibitory. Allicin induced activation of extracellular signal-regulated kinases 1 and 2 (ERK1/2) in human peripheral mononuclear cells, and also in wild-type Jurkat T-cells. Allicin failed to activate ERK1/2 in Jurkat T cells that express p21(ras), in which Cys118 was replaced by Ser. These cells are not susceptible to redox-stress modification and activation. We postulate that the immune stimulatory effect of allicin is mediated by redox-sensitive signaling such as activation of p21(ras). It is suggested that the antitumor effect of allicin is related to its immune-stimulatory properties.
Patya
Miriam
M
Felsenstein Medical Research Center, Sackler Faculty of Medicine-Tel Aviv University, Rabin Medical Center-Beilinson Campus, Petah-Tikva 49100, Israel.
Zahalka
Muayad A
MA
Vanichkin
Alexey
A
Rabinkov
Aharon
A
Miron
Talia
T
Mirelman
David
D
Wilchek
Meir
M
Lander
Harry M
HM
Novogrodsky
Abraham
A
D019943:Amino Acid Substitution; D000818:Animals; D000890:Anti-Infective Agents / Q000494:pharmacology*; D003602:Cytotoxicity, Immunologic; D004220:Disulfides; D004789:Enzyme Activation / Q000187:drug effects; D006801:Humans; D019169:Jurkat Cells; D008213:Lymphocyte Activation / Q000187:drug effects*; D008264:Macrophages / Q000276:immunology / Q000378:metabolism; D051379:Mice; D008810:Mice, Inbred C57BL; D009374:Neoplasms, Experimental / Q000188:drug therapy* / Q000276:immunology; D015689:Oncogene Protein p21(ras) / Q000235:genetics / Q000378:metabolism*; D010084:Oxidation-Reduction / Q000187:drug effects; D015398:Signal Transduction / Q000187:drug effects / Q000235:genetics; D013441:Sulfinic Acids / Q000494:pharmacology*; D013601:T-Lymphocytes / Q000187:drug effects / Q000276:immunology*
D000890:Anti-Infective Agents; D004220:Disulfides; D013441:Sulfinic Acids; C006452:allicin; D015689:Oncogene Protein p21(ras)