Abstract
Daidzein (Da), a major soy isoflavone, had been shown to induce differentiation in the murine neuroblastoma Neuro-2a (BU-1) cells mediated by estrogen receptor, and other health effects, such as reduction of tumour invasivenss and immunomodulatory effect. In this study, we compared the effects and signaling mechanisms of differentiation inducers (DIs) Da, all-trans retinoic acid (ATRA) and prostaglandin E2 (PGE2), in BU-1 cells. Da, ATRA, and PGE2 could inhibit the growth of BU-1 cells. Cell cycle analysis indicated that Da reduced cells at the G2/M phase of the cell cycle; while both ATRA and PGE2 caused a G2/M phase arrest. Cell death studies found that Da but not ATRA or PGE2 induced apoptosis; where PGE2 exerted anti-apoptotic effect in the cells. All the DIs triggered neurite outgrowth; however, only Da and ATRA could elicit functional differentiation as indicated by elevated acetylcholine esterase activity. The crosstalk of cellular response signaling was probed by the inhibition of MAPK pathways. The inhibition of p38 MAPK and ERK pathways suppressed the growth inhibition induced by ATRA: p38 MAPK inhibition was coupled with cell differentiation and ERK inhibition was linked to cell cycle modulation. In PGE2-treated cells, the inhibition of ERK pathway potentiated the growth inhibition, reduced cells at the S phase, and suppressed the anti-apoptotic effect of PGE2. The effects Da were independent of MAPK activities. Our results suggested that daidzein has distinct properties from other DIs, which might pose some novel therapeutic possibilities. [J Physiol Sci. 2007;57 Suppl:S118]
