Effects of Korean mistletoe lectin (Viscum album coloratum) on proliferation and cytokine expression in human peripheral blood mononuclear cells and T-lymphocytes.
The anti-cancer activity of mistletoe has been ascribed to a combination of cytotoxic and immunological effects. We previously showed that Korean mistletoe lectin (Viscum album L. var. coloratum agglutinin, VCA) can stimulate IFN-gamma production and modulate proliferation in murine splenocytes. In this study, we investigated the effects of VCA on human peripheral blood mononuclear cells (hPBMC) and T-lymphocytes. The addition of VCA resulted in a significant inhibition of proliferation at higher concentrations (at 2-8 ng/mL, 1-8 ng/mL in hPBMC and T-lymphocytes, respectively) but an induction at lower concentrations (at 4-16 pg/mL, 4-32 pg/mL in hPBMC and T-lymphocytes, respectively). Further studies were carried out to determine if the pro-proliferative or anti-proliferative activity exhibited by VCA was correlated with apoptosis and cytokine secretion. As a result, the apoptotic cell number increased to 26% after 48 h of VCA treatment (10 ng/mL) in the presence of anti-CD3/CD28 antibodies. On the other hand, without anti-CD3/CD28 antibody stimulants, VCA did not arrest cell cycle. In addition, it was shown that VCA could induce IL-2 secretion was dose-dependently increased by VCA in stimulated (anti-CD3/CD28 antibodies) (at 0.25-2 ng/mL) and non-stimulated (at 3-25 pg/mL) human T-lymphocytes. Also, at low and non-toxic concentrations of VCA, the RT-PCR result confirmed the release of pro-inflammatory cytokines such as IL-1alpha, IL-1beta, IL-6, IL-8, and IFN-gamma. These data may suggest new perspective to modulate the balance between cell growth, cytokine production and programmed cell death therapeutically.
Lyu
Su-Yun
SY
Immune Modulation Research Group, School of Pharmacy, University of Nottingham, University Park, Nottingham, NG7 2RD, UK.
Park
Won-Bong
WB
D000906:Antibodies; D000972:Antineoplastic Agents, Phytogenic / Q000737:chemistry / Q000302:isolation & purification / Q000494:pharmacology*; D017209:Apoptosis / Q000187:drug effects; D018106:CD28 Antigens / Q000276:immunology; D017252:CD3 Complex / Q000276:immunology; D049109:Cell Proliferation / Q000187:drug effects*; D002470:Cell Survival / Q000187:drug effects; D002478:Cells, Cultured; D016207:Cytokines / Q000235:genetics / Q000378:metabolism*; D004305:Dose-Response Relationship, Drug; D006384:Hemagglutination / Q000187:drug effects; D006386:Hemagglutination Tests; D006801:Humans; D007376:Interleukin-2 / Q000378:metabolism; D007963:Leukocytes, Mononuclear / Q000187:drug effects* / Q000276:immunology / Q000378:metabolism / Q000473:pathology; D008213:Lymphocyte Activation / Q000187:drug effects*; D008970:Molecular Weight; D037121:Plant Lectins / Q000737:chemistry / Q000302:isolation & purification / Q000494:pharmacology*; D028321:Plant Preparations / Q000494:pharmacology; D012333:RNA, Messenger / Q000378:metabolism; D013601:T-Lymphocytes / Q000187:drug effects* / Q000276:immunology / Q000378:metabolism / Q000473:pathology; D013997:Time Factors; D028182:Viscum album / Q000737:chemistry
D000906:Antibodies; D000972:Antineoplastic Agents, Phytogenic; D018106:CD28 Antigens; D017252:CD3 Complex; D016207:Cytokines; D007376:Interleukin-2; D037121:Plant Lectins; D028321:Plant Preparations; D012333:RNA, Messenger