Cancer cells are highly dependent on glycolysis to supply the energy and intermediates required for cell growth and proliferation. The
enzyme 6-phosphofructo-1-kinase (PFK) is critical for glycolysis, and its activity is directly correlated with cellular
glucose consumption.
Resveratrol is a potential anti-tumoral drug that decreases
glucose metabolism and viability in
cancer cells. However, the mechanism involved in
resveratrol-mediated anti-
tumor activity is not entirely clear. In this work, it is demonstrated that
resveratrol decreases viability,
glucose consumption and
ATP content in the human
breast cancer cell line MCF-7. These effects are directly correlated with PFK inhibition by
resveratrol in these cells. Moreover,
resveratrol directly inhibits purified PFK, promoting the dissociation of the
enzyme from fully active tetramers into less active dimers. This effect is exacerbated by known negative regulators of the
enzyme, such as
ATP and
citrate. On the other hand, positive modulators that stabilize the tetrameric form of the
enzyme, such as fructose-2,6-bisphosphate and
ADP, prevent the inhibition of PFK activity by
resveratrol, an effect not observed with increased pH. In summary, our results provide evidence that
resveratrol directly inhibits PFK activity, therefore disrupting
glucose metabolism and reducing viability in
cancer cells.