A hypothetical model for action of soybean isoflavonoids against cancer involving a shift to proline-linked energy metabolism through activation of the pentose-phosphate pathway
2004
McCue, P. | Shetty, K.
Soybean isoflavonoids and related phenolic antioxidants from other dietary plant species have long been associated with numerous biological activities linked to the chemoprevention of cancers and oxidation-linked diseases. But until now, no mechanisms or models have been put forth to explain how all of these activities of dietary phenolics could work together to promote health and protect from disease. Here, we present a hypothetical model based on the soybean isoflavonoid genistein for the beneficial action of dietary phenolic antioxidants that incorporates not only the known molecular activities, but also the known metabolic effects that dietary phenolics have on cellular systems such as energy metabolism and the antioxidant enzyme response to reactive oxygen species. Our model presents in a clear manner how a cancerous cell, although mutated and dysfunctional on both biochemical and genetic levels, cannot escape its beginnings as a normal cell and the underlying response mechanisms that are retained from that heritage. By our model, we present how dietary phenolics such as genistein may trigger a switch in energy metabolism from an NADH-supported system to one supported by proline (via the proline-linked pentose-phosphate pathway) through the activation of a stress-response mechanism known to occur in normal cells during stress conditions and which may still remain in cancerous cells. Further, we postulate how an inability of cancer cells to disengage this stress response-induced change in energy metabolism due to biochemical and/or genetic mutations could result in the death of the diseased cell. This metabolic model has implications for the further understanding of how dietary phenolics may confer their beneficial effects and also for the design of chemopreventive agents and functional foods.
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