Ranolazine as a protective agent against Lung Cancer: A translational approach

Abstract

Lung cancer is a malignant lung tumor characterized by uncontrolled cell growth. Ranolazine is an anti-anginal drug which shows its effect by inhibiting latent sodium channel. The aim of this study was to evaluate the protective effect of Ranolazine on urethane induced lung cancer in BALB/c mice. In silico molecular docking studies and in vitro HDAC2 assay was performed against human HDAC2 protein. MTT assay was assessed against A549 & HepG2 cell lines to corroborate, in vivo study was done where urethane was administered 0.5 mg/gm i.p twice a week for a period of 4 weeks, Ranolazine 50 mg/kg, 100 mg/kg p.o daily as low and high dose respectively and methotrexate as standard 0.5 mg/kg p.o. toward the end of 5th week various antioxidant parameters like MDA, GSH, CAT, SOD, were estimated and excise lung tissue was subjected to histopathological evaluation. The molecular interaction of ranolazine with HDAC2 enzyme were also supported by molecular docking simulations. In vitro MTT revealed higher Cytotoxicity in A549 (IC50 209.43 g/ml) compared to HepG2 (IC50 236.87 g/ml). In the present study on treatment with Ranolazine (50 & 100 mg/kg, p.o) antioxidant marker like MDA, GSH, CAT, SOD was significantly altered. In conclusion present study suggests that treatment with ranolazine has shown protective effect on urethane induced lung cancer in mice.