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.

Resveratrol promotes regression of renal carcinoma cells via a renin-angiotensin system suppression-dependent mechanism

“…As a type of free radical scavenger and antioxidant, resveratrol is recognized as an effective anticancer compound in several types of cancer, such as leukemia (28), breast (29–32), prostate (33) and ovarian cancers (34), melanoma (35) and primary brain tumors (36). In the present study, it was found that resveratrol may suppress renal carcinoma cell growth in a time- and dose-dependent manner.…”

Cancer as a disorder of patterning information: computational and biophysical perspectives on the cancer problem

“…Unbiased drug screens for inhibitors of cancer stem cells have implicated potassium ionophores such as salinomycin [358], and tetraethylammonium (TEA, a potassium channel blocker), was found to suppress colony formation in endometrial cancer cells while withdrawal of TEA resulted in a significant enhancement of tumorigenesis [359]. Known cancer-fighting agents are now beginning to be recognized as ion channel modulators, for example resveratrol [360][361][362]. Indeed, drugs that target membrane voltage-generating transporters have already shown clinical promise in cancer [363].…”

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“…[20] In addition, resveratrol has shown to attenuate several voltage gated ion channels in several cell lines. Mainly resveratrol inhibited voltage gated sodium current in rat prostate cancer cell line (MAT-LyLu) [11] and Kv1.3 in human lymphocytes. [21] Our obtained result shows that perfusion of 200 µM of resveratrol inhibited I K current in LNCaP cells.…”

“…Especially curcumin and resveratrol exerts a modulatory effect on several ion channels, including voltage gated sodium and potassium channels. [11][12][13] However, to date, no studies investigated the modulatory effect of phenolic compounds curcumin, resveratrol, rutin, and troxerutin on voltage gated K + channel in human prostate cancer cell line LNCaP.…”