The common observation that
cancer cells present higher glycolytic rates when compared to control cells leads to the proposal of glycolysis as a potential target for the development of anti-tumoral agents. Anti-inflammatory drugs, such as
acetylsalicylic acid (ASA) and
salicylic acid (SA), present anti-tumoral properties, inducing apoptosis and altering
tumor glucose utilization. The present work aims at evaluating whether ASA could directly decrease cell glycolysis through inhibition of the major regulatory
enzyme within this pathway,
6-phosphofructo-1-kinase (PFK). We show that ASA and SA inhibit purified PFK in a dose-dependent manner, and that this inhibition occurs due to the modulation of the
enzyme quaternary structure. ASA and SA promote the dissociation of the
enzyme active tetramers into quite inactive dimers, a common regulatory mechanism of this
enzyme. The inhibitory effects of ASA and SA on PFK are fully reversible and can be prevented or reverted by the binding of the
enzyme to the actin filaments. Both drugs are also able to decrease
glucose consumption by human
breast cancer cell line MCF-7, as well as its viability, which decrease parallelly to the inhibition of PFK on these cells. In the end, we demonstrate the ability of ASA and SA to directly modulate an important regulatory intracellular
enzyme, and propose that this is one of their mechanisms promoting anti-tumoral effects.