Saponins in soy reduce NNK-induced lung cancer by increasing plasma isoflavone levels

Recently, we found, using a cigarette carcinogen-induced lung cancer model, that soy protein isolate (SPI) was superior to casein in preventing lung cancer. In this study, we have attempted to identify the component(s) within SPI responsible for this chemopreventive effect. We fractionated the SPI using ethanol to separate the ethanol-soluble fraction (ESF) and the washed SPI and compared their efficacy to diets made with amino acids that comprise soy protein or casein, in preventing lung tumor formation in A/J mice. Only the ethanol-soluble fraction was as effective as SPI in preventing lung tumor formation. Since isoflavones and saponins are known ethanol-soluble bioactives from soy, we added isoflavones, or saponins or both to casein and found that isoflavones or saponins alone did not reduce lung nodule formation. However, when we combined soy saponins and isoflavones, we saw a significant (P < 0.05) reduction in NNK-induced lung nodules, and an increase in plasma isoflavone levels, suggesting that the saponins may enhance the bioavailability of the isoflavones in these mice. Taken together, we suggest that the superior efficacy of SPI over casein could be attributed, at least in part, to the synergistic effect of the soy saponins and isoflavones.