GLIS, a bioactive proteoglycan fraction from Ganoderma lucidum, displays anti-tumour activity by increasing both humoral and cellular immune response.
OBJECTIVE
Ganoderma lucidum, a traditional Chinese medicine, is well known as a modulator of functions of the immune system as well as an anti-tumour agent. However, its active compounds and their molecular mechanisms of action are not well established. GLIS, a proteoglycan isolated from the fruiting body of G. lucidum, stimulates directly the activation of B lymphocytes. In this work, the immunoactivation capacities of GLIS as well as its anti-tumour effect were investigated in vitro and in vivo.


METHODS
Tumour-bearing mice were prepared by inoculation of mouse sarcoma S180 cells into BALB/c mice. Lymphocytes and bone marrow-derived macrophages were isolated from spleen and tibia/femurs, respectively. After stimulation with GLIS different immune responses of these cells were analysed. Anti-tumour effect of GLIS was determined.


RESULTS
After treatment with GLIS, spleen-derived B lymphocytes from tumour-bearing mice became activated, proliferated and produced large amounts of immunoglobulins. Bone marrow-derived macrophages from tumour-bearing mice also became activated after exposure to GLIS, and they produced important immunomodulatory substances, such as IL-1β, TNF-α and reactive nitrogen intermediates, like NO. GLIS markedly increased phagocytosis of macrophages, and very importantly, it markedly raised the macrophage-mediated tumour cytotoxicity. Treatment of mice with GLIS caused an inhibition of mouse sarcoma S180 tumour growth by 60% in vivo.


CONCLUSIONS
These results indicate that GLIS exhibits a capacity to increase remarkably both humoral and cellular immune activities of tumour-bearing mice and inhibits tumour growth significantly. The anti-tumour effect of GLIS results from its capacity to increase the host's immune activity.
Zhang
Jingsong
J
Institut für Biochemie und Molekularbiologie, CBF, Charité-Universitätsmedizin Berlin, Germany.
Tang
Qingjiu
Q
Zhou
Changyan
C
Jia
Wei
W
Da Silva
Luis
L
Nguyen
Long Duc
LD
Reutter
Werner
W
Fan
Hua
H
D000818:Animals; D000970:Antineoplastic Agents / Q000276:immunology / Q000494:pharmacology*; D001402:B-Lymphocytes / Q000187:drug effects / Q000276:immunology; D005656:Fungal Proteins / Q000276:immunology / Q000494:pharmacology*; D007111:Immunity, Cellular / Q000187:drug effects*; D056724:Immunity, Humoral / Q000187:drug effects*; D053583:Interleukin-1beta / Q000187:drug effects / Q000276:immunology; D008264:Macrophages / Q000187:drug effects / Q000276:immunology; D008516:Medicine, Chinese Traditional; D051379:Mice; D008807:Mice, Inbred BALB C; D009569:Nitric Oxide / Q000378:metabolism; D011509:Proteoglycans / Q000276:immunology / Q000494:pharmacology*; D012510:Sarcoma 180 / Q000188:drug therapy* / Q000276:immunology / Q000473:pathology; D014409:Tumor Necrosis Factor-alpha / Q000187:drug effects / Q000276:immunology
D000970:Antineoplastic Agents; D005656:Fungal Proteins; C465125:GLIS protein, Ganoderma lucidum; D053583:Interleukin-1beta; D011509:Proteoglycans; D014409:Tumor Necrosis Factor-alpha; D009569:Nitric Oxide