Resveratrol: Inhibitory Effects on Metastatic Cell Behaviors and Voltage-Gated Na⁺ Channel Activity in Rat Prostate Cancer In Vitro

Abstract

Resveratrol, a natural plant phenolic found at high concentration in red grapes, has been suggested to have a range of health benefits. Here, we tested its effects on metastatic cell behaviors. The strongly metastatic rat prostate MAT-LyLu cells were used as a model. At 20 μM, resveratrol had no effect on cellular proliferation or viability. However, it suppressed significantly 1) lateral motility by up to 25%; 2) transverse motility by 31%; and invasion by 37%. It also increased the cells’ adhesion to substrate by 55%. Electrophysiologically, resveratrol inhibited voltage-gated Na⁺ channel (VGSC) activity that has been shown previously to promote metastatic cell behaviors. This effect was dose-dependent with an IC₅₀ of ∼50 μM. Voltage dependencies of current activation and peak were not affected but steady-state inactivation was shifted to more hyperpolarized potentials and recovery from inactivation was slowed. Coapplication of resveratrol with the highly specific VGSC blocker tetrodotoxin did not result in any additive effect on inhibition of both 1) VGSC activity and 2) metastatic cell behaviors. These results suggest 1) that a significant mode of action of resveratrol is VGSC blockage and 2) that resveratrol has promise as a natural antimetastatic agent.

Additional information

Funding

We would like to acknowledge continued financial support from the Pro Cancer Research Fund in the form of a rolling grant and The Stanley Foundation (Mustafa Bilgin Ali Djamgoz, Scott Paton Fraser).