Over-expression of K+ channels has been reported in human cancers
and is associated with the poor prognosis of several malignancies. EAG1,
a particular potassium ion channel, is widely expressed in the brain
but poorly expressed in other normal tissues. Kunitz proteins are
dominant in metazoan including the dog tapeworm, Echinococcus
granulosus. Using computational analyses on one A-type potassium
channel, EAG1, and in vitro cellular methods, including major cancer
cell biomarkers expression, immunocytochemistry and whole-cell patch
clamp, we demonstrated the anti-tumor activity of three synthetic small
peptides derived from E. granulosus Kunitz4 protease inhibitors.
Experiments showed induced significant apoptosis and inhibition of
proliferation in both cancer cell lines via disruption in cell-cycle
transition from the G0/G1 to S phase. Western blotting showed that the
levels of cell cycle-related proteins including P27 and P53 were altered
upon kunitz4-a and kunitz4-c treatment. Patch clamp analysis
demonstrated a significant increase in spontaneous firing frequency in
Purkinje neurons, and exposure to kunitz4-c was associated with an
increase in the number of rebound action potentials after hyperpolarized
current. This noteworthy component in nature could act as an ion
channel blocker and is a potential candidate for cancer chemotherapy
based on potassium channel blockage.