Soybean isoflavones, genistein and genistin, inhibit rat myoblast proliferation, fusion and myotube protein synthesis

The isoflavones, genistein and genistin, are cytotoxic in vitro (e.g., inhi bition of cell proliferation), due in part to inhibition of protein tyrosin e kinase and DNA topoisomerase activities. Normal cell functions associated with these enzymatic activities could potentially be impaired in animals t hrough ingestion of soybean products. In this study, cultured rat myogenic cells (L8) were used to determine whether genistein or genistin influences myoblast proliferation and fusion, and myotube protein synthesis and degrad ation. Genistein or genistin was dissolved in dimethylsulfoxide and include d in the culture medium at 0, 1, 10 or 100 mu mol/L. Myoblast proliferation was measured by methyl-H-3-thymidine incorporation over 48 h. Myoblast dif ferentiation was evaluated by the number of nuclei in multinucleated myotub es. Myotube protein synthesis was measured by 2-h H-3-amino acid incorporat ion into the myosin and total protein pools after acute (2 h) or chronic (2 4 h) exposure to similar treatments; protein degradation was measured by me asuring radioactivity in protein pools following a time course of protein b reakdown after myotube proteins were prelabeled with H-3-amino acids. Genis tein or genistin strongly inhibited in vitro myoblast proliferation (P < 0. 001) and fusion (P < 0.001) in a dose-dependent manner with effective genis tein concentration as low as 1 mu mol/L. Genistein or genistin inhibited pr otein accretion in myotubes (P < 0.001). Decreased protein accretion is lar gely a result of inhibition on cellular (myofibrillar) protein synthesis ra te. No adverse effect on protein degradation was observed. Results suggest that if sufficient circulating concentrations are reached in tissues of ani mals consuming soy products, genistein/genistin can potentially affect norm al muscle growth and development.