Stimulation of host resistance against tumors by glycyrrhizin, an active component of licorice roots.
The effect of glycyrrhizin (GR), a Chinese herbal drug extracted from licorice roots, on the host resistance to tumors was investigated in a murine system. Administration of GR to BALB/c mice, which were inoculated s.c. with 1 x 10(6) cells/mouse of Meth A tumors, resulted in either no antitumor effect (8/20, 40%), a delay in tumor growth (9/20, 45%), or elimination of tumor growth (3/20, 15%) in these mice. In addition, the incidence of Meth A solid tumors was inhibited by GR when mice were inoculated with 1.5 x 10(4) cells/mouse or less of Meth A tumor cells, but not 7.5 x 10(4) cells/mouse or more. These results indicate that in this murine tumor system GR has a very weak antitumor effect. When GR at a dose of 20 mg/kg was administered to mice immunized with allogeneic lymphocytes 1 to 9 days after the immunization, the generation of suppressor macrophages (S-M phi) was clearly reduced as compared with that of S-M phi generated in immunized controls. In addition, when allospecific CTL (allo-CTL), which were generated in alloimmunized mice treated with GR followed by in vitro stimulation with allogeneic lymphocytes in a mixed lymphocyte reaction, were adoptively transferred to tumor-bearing mice treated with GR, the antitumor activity of allo-CTL derived from immunized mice treated with GR was markedly enhanced as compared with that of allo-CTL from immunized mice. Furthermore, established solid tumors were completely eliminated when interleukin-2 immunotherapy was performed in these mice in combination with GR treatments, but not interleukin-2 or GR alone.(ABSTRACT TRUNCATED AT 250 WORDS)
Suzuki
F
F
Department of Internal Medicine, University of Texas Medical Branch, Galveston 77555-0882.
Schmitt
D A
DA
Utsunomiya
T
T
Pollard
R B
RB
D000818:Animals; D005260:Female; D006034:Glycyrrhetinic Acid / Q000031:analogs & derivatives* / Q000494:pharmacology / Q000627:therapeutic use; D019695:Glycyrrhizic Acid; D007108:Immune Tolerance / Q000187:drug effects; D007114:Immunization; D007167:Immunotherapy; D016219:Immunotherapy, Adoptive; D007376:Interleukin-2 / Q000627:therapeutic use; D008264:Macrophages / Q000187:drug effects* / Q000276:immunology; D051379:Mice; D008807:Mice, Inbred BALB C / Q000276:immunology; D008810:Mice, Inbred C57BL / Q000276:immunology; D009368:Neoplasm Transplantation; D012513:Sarcoma, Experimental / Q000276:immunology / Q000628:therapy*; D013154:Spleen / Q000276:immunology; D013602:T-Lymphocytes, Cytotoxic / Q000276:immunology / Q000637:transplantation
D007376:Interleukin-2; D019695:Glycyrrhizic Acid; D006034:Glycyrrhetinic Acid