Effect of polyphenols on glucose and lactate transport by breast cancer cells.
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-"aerobic lactatogenesis". Accordingly, GLUT1 and MCT1, which are the main glucose and lactate transporters in cancer cells, respectively, have been proposed as oncogenes and are currently seen as potential therapeutic targets in cancer treatment. Polyphenols, commonly contained in fruits and vegetables, have long been associated with a protective role against cancer. Generally considered as nontoxic, dietary polyphenols are considered ideal chemopreventive and possibly chemotherapeutic agents. Several mechanisms of action of polyphenols in breast cancer cells have been proposed including modulation of intracellular signaling, induction of apoptosis through redox regulation or modulation of epigenetic alterations. Additionally, in vitro studies have shown that several polyphenols act as specific inhibitors of glucose transport in breast cancer cell lines and an association between their anticarcinogenic effect and inhibition of glucose cellular uptake has been described. Also, some polyphenols were found to inhibit lactate transport. Importantly, some polyphenols behave as inhibitors of both glucose and lactate cellular uptake by breast cancer cells and 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 suppliers. 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.
Department of Biochemistry, Faculty of Medicine, University of Porto, Al. Prof. Hernâni Monteiro, 4200-319, Porto, Portugal. fmartel@med.up.pt.|Instituto de Investigação e Inovação em Saúde, Universidade do Porto, Porto, Portugal. fmartel@med.up.pt.
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Martel
Department of Biochemistry, Faculty of Medicine, University of Porto, Al. Prof. Hernâni Monteiro, 4200-319, Porto, Portugal.
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Guedes
Department of Biochemistry, Faculty of Medicine, University of Porto, Al. Prof. Hernâni Monteiro, 4200-319, Porto, Portugal.|CINTESIS, Center for Research in Health Technologies and Information Systems, University of Porto, 4200-319, Porto, Portugal.
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D000970:Antineoplastic Agents / Q000494:pharmacology* / Q000627:therapeutic use; D001692:Biological Transport / Q000187:drug effects; D001943:Breast Neoplasms / Q000188:drug therapy / Q000378:metabolism* / Q000517:prevention & control; D045744:Cell Line, Tumor; D005260:Female; D015972:Gene Expression Regulation, Neoplastic / Q000187:drug effects; D005947:Glucose / Q000378:metabolism*; D051272:Glucose Transporter Type 1 / Q000378:metabolism; D006801:Humans; D019344:Lactic Acid / Q000378:metabolism*; D027501:Monocarboxylic Acid Transporters / Q000378:metabolism; D059808:Polyphenols / Q000494:pharmacology* / Q000627:therapeutic use; D027981:Symporters / Q000378:metabolism; D000099233:Monocarboxylate Transport Protein 1
D000970:Antineoplastic Agents; D005947:Glucose; D051272:Glucose Transporter Type 1; D019344:Lactic Acid; D027501:Monocarboxylic Acid Transporters; D059808:Polyphenols; D027981:Symporters; D000099233:Monocarboxylate Transport Protein 1; C495677:SLC2A1 protein, human
Aerobic lactatogenesis; Breast cancer; Glucose transport; Lactate transport; Polyphenols