EFFECT OF POLYPHENOLS ON NUTRIENT UPTAKE BY BREAST CANCER CELLS:A NEW POTENTIAL THERAPEUTIC APPROACH?

Abstract

One of the cancer molecular hallmarks is a deviant energetic metabolism, known as the Warburg effect, whereby the rate of glucose uptake is significantly increased and a high rate of glycolysis and lactic acid production occurs even when oxygen is present. Accordingly, GLUT1 and MCT1, which are the main glucose and lactate membrane transporters in cancer cells, respectively, have been proposed as oncogenes and are currently seen as potential therapeutic targets in cancer treatment. Polyphenols are associated with a protective role against cancer. In relation to breast cancer, several mechanisms of action of polyphenols are known to contribute to their anticarcinogenic effect, including modulation of intracellular signaling, induction of apoptosis or epigenetic alterations. Additionally, several polyphenols are able to inhibit glucose transport in breast cancer cell lines; interestingly enough, an association between inhibition of glucose cellular uptake and their anticarcinogenic effect has been described. Also, some polyphenols are able to inhibit lactate transport. Importantly, some polyphenols behave as inhibitors of both glucose and lactate cellular uptake by breast cancer cells. These compounds are thus very interesting in the context of a chemopreventive effect, because they deplete breast cancer cells of their two most important energy sources. So, the antimetabolic effect of polyphenols should be regarded as a mechanism of action contributing to their chemopreventive/chemotherapeutic potential in relation to breast cancer.