Human
breast cancer tissues, as well as normal tissues from the same patients, were treated with
clotrimazole (CTZ) and have their capacities for
glucose consumption and
lactate production evaluated. This treatment strongly decreased the
lactate production rate by
tumor tissues (85% inhibition) without affecting the other measurements made, i.e.
lactate production by control tissues or
glucose consumption by both, control and
tumor tissues. This result directly correlates with the inhibition promoted by CTZ on the activity of the major regulatory glycolytic
enzyme 6-phosphofructo-1-kinase (PFK) that was observed in
tumor tissues (84% inhibition) but not in control tissues. Fractionation of the tissues revealed that this inhibition does not occur in the soluble fraction of the
enzyme, but is exclusive of a particulate fraction. It has been previously shown that the particulate fraction of PFK activity in
tumors is associated to actin filaments (
f-actin). Thus, we investigated whether CTZ would affect the association between PFK and
f-actin and we found that the
drug directly induces the dissociation of the two
proteins in the same extent that it inhibits
lactate production, total PFK activity and the particulate PFK activity. We concluded that CTZ disrupts glycolysis on human
breast tumor tissues, inhibiting PFK activity by dissociating the
enzyme from
f-actin.