Low-Glycotoxin Diets and Spirulina may have Potential for Slowing the Growth and Spread of Rage-expressing Cancers

Abstract

A number of recent studies indicate that many cancers express receptors for advanced glycation end products (RAGEs), and that stimulation of these receptors make these cancers more invasive and, in some cases, boosts their proliferation. In some of these cancers, autocrine production of protein agonists for RAGE (HMGB1, S1100A) promotes their spread; the typically aggressive growth of cancers in diabetics may reflect activation of RAGE by endogenously produced advanced glycation end products (AGEs). But RAGE can also be activated by dietary “glycotoxins” – compounds produced by Maillard reactions in highly heated foods that are structurally and functionally similar to AGEs produced in diabetics. In rodents, dietary glycotoxins promote oxidative stress and pathologies linked to oxidative stress, presumably via RAGE activation. These considerations suggest that low-glycotoxin diets may have potential for slowing the spread of certain cancers expressing RAGE, a proposition that can readily be tested in rodent tumor models. Guidelines for achieving such diets have been published; low-fat foods of plant origin are typically low in glycotoxins, and the glycotoxin content of animal products and fatty plant products can be minimized by cooking at low heat (e.g. boiling, steaming). It may also be feasible to suppress the downstream signaling of RAGE in cancers by inhibiting the activity of NADPH oxidase, which appears to be the chief source of the oxidative stress triggered by RAGE; a role for NADPH oxidase in the aggressive growth of many cancers has been established. By mimicking the physiological antioxidant role of free bilirubin, the phycocyanobilin richly supplied by spirulina has the potential to down-regulate NADPH oxidase activity, and thereby impede RAGE signaling.