Pharmacological targeting of Kv1.3 in pancreatic cancer cells

The voltage-gated potassium channel Kv1.3 has been shown to have an altered expression in several cancer tissues compared to normal ones, like in human pancreatic cancer. Pharmacological inhibition of the mitochondrial Kv1.3 by membrane-permeant inhibitors such as PAPTP, triggers membrane potential changes, ROS production and cytochrome C release, triggering apoptotic events and can selectively kill cancer cells, sparing healthy ones. We here describe that combination treatment of PAPTP with a commonly used cytotoxic chemotherapy agent used in the treatment of pancreatic cancer, and a clinically used modulator of Bcl-2 family proteins show an enhanced ability to kill pancreatic cancer cells. The possible mechanism of this synergy has also been investigated. Our results suggest that this combination treatment could represent an innovative therapeutic strategy against pancreas cancer.