In vitro and in silico therapeutic potential of Nyctanthes arbor-tristis (L.) flower extract against prostate cancer

Prostate cancer (PCa) is a serious clinical problem because of metastatic development and the adverse effect of conventional treatment. This paper explores the anticancer effects of Nyctanthes arbor-tristis (L.) flower extract (NAFE) against PC3 and LNCaP cells. NAFE was profiled by high resolution liquid chromatography coupled to mass spectrometry, which led to the identification of fourteen major phytochemicals of potential relevance. Computational Molecular Docking (MD), Molecular Dynamics Simulation (MDS) and ADME/T was used to predict the underlying probable mechanism of its anticancer properties. Assays showed that NAFE exerts a dose-dependent inhibition of cellular proliferation with a maximal inhibition level around 74% and has cytostatic activity based on a modest increase in the G1-phase cell population. Western blotting evaluation suggest the downregulation of key regulatory proteins such as Cyclin D1, CDK4/6, phosphorylated Epidermal Growth Factor Receptor (EGFR) and phosphorylated Akt. Furthermore, NAFE impedes migration and invasion of PC3 PCa cells which was revealed by a reduction of 73.7% in wound healing assays, accompanied by suppression of matrix metalloproteinases (MMP-2 and MMP-9). In silico MD analyses and MDS study identified Phloridzin as probable lead molecule targeting EGFR (-138.51 kcal/mol), CDK6 (-140.64 kcal/mol), CDK4 (-130.633 kcal/mol) and MMP2 (-138.028 kcal/mol) proteins supported by favorable ADME/T parameters. The present findings establish the potential of NAFE as a non-toxic, nutraceutical candidate having therapeutic potential for efficient management of metastatic PCa.