Phytocompounds screening of Nigella sativa in terms of human cancer by targeting sphingosine kinase-1 and pyruvate kinase-M2: a study based on in silico analysis.

Cancer is a multifactorial disease that can cause morbidity and mortality in humans. An altered gene expression in cancer leads to a change in the overall activity of the human cell. Overexpression of cancer protein may give a piece of wide information about the specific type of tumor. Sphingosine kinase-1 (SK-1) is a metabolic enzyme that is mainly overexpressed in several types of cancer and other inflammatory diseases. Similarly, pyruvate kinase-M2 (PK-M2) is an important oncogenic ATP-producing glycolytic enzyme that is upregulated in most cancer cells. The phytocompound of medicinal plants such as Nigella sativa contains a variety of micronutrients that inhibit the proliferation and activity of tumor cells. In this study, the role of phytocompounds in combating cancer was studied against the model kinase proteins, that is, PK-M2 and SK-1. In silico tool like the PASS-Way2Drug server was used to predict the anticancer properties of phytocompounds. Moreover, the CLC-Pred web server provided the cytotoxicity prediction of chemical compounds against several human cancer cell lines. The pharmacokinetics and toxicity profiles were predicted by the SwissADME and pkCSM software. The binding energies were obtained by molecular docking to confirm the intermolecular interaction of selected phytocompounds with proteins. Consequently, molecular dynamics (MD) simulation confirmed the stability, conformational changes, and dynamic behavior of the kinase proteins complexed with the lead phytocompounds, that is, epicatechin, apigenin, and kaempferol.Communicated by Ramaswamy H. Sarma.

Evaluation of DNA interaction, genotoxicity and oxidative stress induced by iron oxide nanoparticles both in vitro and in vivo: attenuation by thymoquinone.

Iron oxide nanoparticles (IONPs) are known to induce cytotoxicity in various cancer cell lines through the generation of reactive oxygen species (ROS). However, the studies on its potential to induce toxicity in normal cell lines and in vivo system are limited and ambiguity still exists. Additionally, small molecules are known to interact with the DNA and cause damage to the DNA. The present study is designed to evaluate the potential interaction of IONPs with DNA along with their other toxicological effects and subsequent attenuation by thymoquinone both in vitro (primary lymphocytes) and in vivo (Wistar rats). IONPs were characterized by TEM, SEM-EDS, and XRD. The results from DNA interaction studies showed that IONPs formed a complex with DNA and also got intercalated between the base pairs of the DNA. The decrease in percent cell viability of rat's lymphocytes was observed along with an increase in ROS generation in a dose-dependent manner (50, 100, 200, 400 and 800 µg/ml of IONPs). The genetic damage in in vivo might be due to the generation of ROS as depletion in anti-enzymatic activity was observed along with an increase in lipid peroxidation in a dose-dependent manner (25, 50, 100 mg/kg of IONPs). Interestingly, supplementation of thymoquinone in combination with IONPs has significantly (P < 0.05) attenuated the genetic and oxidative damage in a dose-dependent manner both in vitro and in vivo. It can be concluded that thymoquinone has the potential to attenuate the oxidative stress and genetic toxicity in vitro and in vivo.