ANTIMETASTATIC AND IMMUNOMODULATING PROPERTIES OF THE WATER EXTRACT FROM CELOSIA-ARGENTEA SEEDS

We have investigated the anti-metastatic effect of Celosia argentea se ed extracts (CAE), which have traditionally been used as a therapeutic drug for eye and hepatic diseases in China and Japan. Intraperitoneal (i.p.) administration of CAE for 7 d before tumor inoculation signifi cantly inhibited liver metastasis caused by intraportal injection of c olon 26-L5 carcinoma cells in a dose-dependent manner. CAE also showed concentration dependent mitogenic activity on BALB/c whole splenocyte s, whereas incubation of the non-adherent fraction of splenocytes with CAE did not induce this activity. CAE has the ability to induce inter leukin (IL)-12 production from macrophages in vitro. Following i.p. ad ministration of CAE the maximal levels of IL-12 and interferon (IFN)-g amma production in serum were achieved at 2-3 and 6 h, respectively. E xperiments using macrophage- or NK cell-deficient mice revealed that C AE-induced IL-12 in serum was not mediated by macrophages and that IFN -gamma production was mainly dependent on natural killer (NK) cells. S ince CAE was inactive when the contributions of macrophages were remov ed in our system, its inhibitory mechanism is likely to be mainly asso ciated with the activation of macrophages to an anti-metastatic state rather than MK cells. CAE administration resulted in increased product ion of IL-2, IFN-gamma and decreased production of a Th2 cytokine (IL- 4) from splenocytes stimulated by PMA and A23187. Thus, the anti-metas tatic effect by CAE is based on its immunomodulating properties includ ing induction of cytokines such as IL-12, IL-2 and IFN-gamma leading t o a Th1 dominant immune state and activating macrophages to the tumori cidal state. This may provide a basis for the inhibition of cancer met astasis.