In vitro Anti-Cancer Activity of Rosuvastatin and Ketorolac Nanoformulations against DDX3

Abstract

Background: DDX3 is the human RNA helicase and enhanced expression of DDX3 protein was found in several cancers including leukemia. Statin family of drugs shown to inhibit the growth of acute myeloid leukemia cells. Objective: In this paper we report the molecular interaction of Rosuvastatin Calcium (RST) salt with DDX3 by Molecular docking. Molecular dynamics simulation (MDS) using Desmond further confirmed that the RST forms strong intra and inter molecular hydrogen bond network with DDX3 as similar to Ketorolac salt, a known inhibitor of DDX3. Materials and methods: To validate the biological activity, RST and KT nanoemulsions were prepared using propylene glycol monocaprylate (type II) NF, glycerol monolinoleate EP, Lauroyl macrogol-6 glycerides EP and poloxamer 188 to improve the bioavailability in rats. Solution state stability study was performed at various pH for 24 h to determine the integrity of RST and KT in nanoemulsion formulations. The prepared formulations have been evaluated for permeability across porcine buccal membrane. The RST and KT nanoemulsions were evaluated for anticancer activity using K-562 leukaemia cancer cell lines. Results: It showed both the nanoemulsions inhibited the growth of the cancer cell and also reduced the expression of DDX3 protein. Bioavailability study in rats revealed that nanoemulsion formulations have exhibited higher systemic concentrations. Conclusion: In summary, taken together, our result demonstrates, for the first time, inhibition of DDX3 expression by RST nanoemulsions indicates that this nanoformulation can be used as an ideal drug candidate to treat DDX3 associated blood cancer. Key words: Rosuvastatin, Ketorolac salt, nanoformulations, DDX3, molecular docking and anti cancer activity.