INDIVIDUAL AND COMBINATORY EFFECTS OF SOY ISOFLAVONES ON THE IN-VITROPOTENTIATION OF LYMPHOCYTE-ACTIVATION

Daidzein and genistein are two prominent soy isoflavones that have bee n reported as promising protectors against cancers at many sites. In a study focusing on the chemopreventive mechanisms, we previously demon strated that daidzein was an effective immune stimulator in an in vivo murine system. In this study we further evaluated the effects of daid zein and genistein, individually and in combination, on in vitro mitog en-stimulated activation of murine lymphocytes. At physiologically rel evant concentrations (0.01-10.0 mu M), daidzein significantly potentia ted proliferation of mixed splenocyte cultures activated with concanav alin A or lipopolysaccharide in a dose-dependent manner in comparison with vehicle control, whereas genistein had no influence on the respon se. Although a significant cooperativity with genistein (1 mu M) was o bserved at low concentrations of daidzein (0.01 mu M) in comparison wi th daidzein alone, genistein failed to augment or counteract the effec ts of high concentrations of daidzein on lymphocyte proliferation. The secretion of cytokine interleukins-2 and -3 from concanavalin A-activ ated lymphocytes was significantly increased again by daidzein and was unaffected or mildly decreased by genistein Taken together, these res ults demonstrate that daidzein, rather than genistein, is able to enha nce in vitro activation of murine lymphocytes and suggest that more st udies focusing on the immunoregulatory mechanism of soy daidzein and t he potential clinical relevance are warranted.