Bioactive food components, cancer cell growth limitation and reversal of glycolytic metabolism.
Cancer cells are resistant to apoptosis and show a shift in energy production from mitochondrial oxidative phosphorylation to cytosolic glycolysis. Apoptosis resistance and metabolic reprogramming are linked in many cancer cells and both processes center on mitochondria. Clearly, mutated cancer cells escape surveillance and turn into selfish cells. However, many of the mechanisms that operate cellular metabolic control still function in cancer cells. This review describes the metabolic importance of glucose and glutamine, glycolytic enzymes, oxygen, growth cofactors and mitochondria and focuses on the potential role of bioactive food components, including micronutrients. The role of B- and A-vitamin cofactors in (mitochondrial) metabolism is highlighted and the cancer protective potential of omega-3 fatty acids and several polyphenols is discussed in relation to metabolic reprogramming, including the mechanisms that may be involved. Furthermore, it is shown that cancer cell growth reduction by limiting the growth cofactor folic acid seems to be associated with reversal of metabolic reprogramming. Altogether, reversal of metabolic reprogramming may be an attractive strategy to increase susceptibility to apoptotic surveillance. Food bioactive components that affect various aspects of metabolism may be important tools to reverse glycolytic to oxidative metabolism and enhance sensitivity to apoptosis. The success of such a strategy may depend on several actors, acting in concert. Growth cofactors may be one of these, which call for careful (re)evaluation of their function in normal and in cancer metabolism.
Keijer
Jaap
J
Human and Animal Physiology, Wageningen University, Wageningen, The Netherlands. Jaap.keijer@wur.nl
Bekkenkamp-Grovenstein
Melissa
M
Venema
Dini
D
Dommels
Yvonne E M
YE
D000818:Animals; D049109:Cell Proliferation; D015536:Down-Regulation; D004734:Energy Metabolism / Q000502:physiology; D005502:Food; D006019:Glycolysis / Q000502:physiology*; D006801:Humans; D008954:Models, Biological; D009369:Neoplasms / Q000178:diet therapy* / Q000378:metabolism* / Q000473:pathology; D009747:Nutritional Physiological Phenomena / Q000502:physiology