Evaluation as NAV1.7 voltage gated sodium channel (VGSC) blocker of ranolazine and riluzole combination

Ion channels are transmembrane proteins located in the cell membrane that open and close, enabling the passage of particulate ions through the membrane. Voltage-gated ion channels (VGSC) from ion channels are, among other cells, expressed by metastatic cancer cells. The cancer cells that are characterized by uncontrolled growth and proliferation form metastases in distant organs are one of the main causes of death from cancer. Increased VGSC expression levels during migration and invasion of prostate, breast and colon cancer cells reveal that they may be new antimetastatic targets. In vitro studies with VGSC have shown that the function of these channels is associated with metastasis of cancer cells, and inhibition of channel function results in inhibition of metastatic activity. Thus, it has been found that these cell movements can be suppressed by agents / drugs that block VGSC. Clinically, Ranolazine (RNL), used in the treatment of angina pectoris, acts by blocking the Na + ion channels and improves diastolic functions in the heart, reducing post-ischemic disorders. In the literature, RNL has been shown to inhibit lateral and transverse movement of cells and reduce lung metastasis. Riluzole (RIL), a neuroprotective drug, is used in ALS disease and acts as a specific VGSC blocker. In human prostate cancer cells, RIL has been shown to inhibit cell proliferation and lateral motility in rat prostate cancer cells. In this study, the effects of antianginal RNL and neuroprotective RIL combination with Na+ channel blocker on Dunning rat prostate cancer model high metastatic Mat-LyLu and low metastatic at-2 cell lineages were evaluated and the relationship between Vgscs and RNL+RIL combination with the antimetastatic target was determined. According to the results, 5 μM + 5 μM concentration of RNL + RIL combination of non-toxic pharmacological agents inhibited proliferation of high metastatic Mat-LyLu cells but did not show an effect on AT-2 cells. RNL, RIL, RNL + RIL concentrations that do not affect cell proliferation were found to occur inhibition of lateral movement / motility of Mat-LyLu cells at 48 hours. This study, which was the first to evaluate the combined effects of RNL and RIL, a VGSC blocker, revealed in vitro that the 2.5 µM+2.5 µM RNL+RIL combination may be effective on lateral cell movement, which plays a role in the progression of prostate cancer cells to metastasis. However, in order to take its place in antimetastatic treatment, the roles of VGSC blocker agents both alone and in combination form need to be investigated both in vitro and in vivo.