Ameliorative Effect of Tapinanthus globiferus on Sodium Arsenite Induced Carcinogenesis in Canton-S strain of Drosophila melanogaster: In-vivo and In-silico Studies

Abstract

Tapinanthus globiferusis a hemi-parasitic plant that grows on vascular trees. It is often regarded as an economic menace due to the damages it cause on trees with economic values. However, despite the perception of the ever-green plant as an economic problem, traditional medicine makes use of the plant in the treatment of different diseases including cancer. This study aimed to investigate the anticancer property of the leaf of Tapinanthus globiferus using Drosophila melanogaster and to identify thepotential anticancer bioactive compounds. To determine a safe dose of the crude extract and fractions of T. globiferusto be used for the studies, thesurvival rates of the flies were evaluated at different concentrations (0, 0.5, 1.0 and 2.0 mg/10 g diet) for 14 days. Carcinogenesis was induced in Drosophila melanogasterusing sodium arsenite (SA) and the SA-exposed flies were treated with 1.0 mg/10 g diet of the three fractions for 10 days. Biochemical parameters of oxidative stress (hydrogen peroxide, non-protein thiol (NPSH), total thiol, nitric oxide, protein carbonyl, malondialdehyde and glutathione-s-transferase (GST) activity), cell viability, negative geotaxis and gene expressions (p53 and Ras) were used to evaluate the ameliorative activityof the fractions on the carcinogenic effects of SA in the flies. HPLC-DAD analysis was carried out to determine the bioactive compounds present in the active fraction. Molecular Docking analysis of the compounds against selected cancer drug targets (VEGF-A and Ras) was done followed by ADMET studies. The results of biochemical analyses showed that the three fractions ameliorated the SA-induced carcinogrnic effects in the flies. The butanol fraction showed higher ameliorative activity. HPLC-DAD results showed the presence of hydroxybenzoate derivatives, hydroxycinnamate derivatives and flavonoids in this fraction. Result of the molecular docking shows that Rutin had higher binding with HsVEFGA with score of -9.793 kcal/mol and with DmVEFGA with score of -8.890 kcal/mol, compared to the standard inhibitor. Also, isoquercetin had higher docking score compared with the standard inhibitor drug of Ras protein of both humans(-8.587 kcal/mol) and Drosophila melanogaster (-11.883 kcal/mol). Both compounds showed low bioavailabilty as drug candidates. While rutin showed class 5 toxicity, isoquercetin showed class 4 toxicity. This suggests that Tapinanthus globiferus may possess potential anticancer attributes that can be associated to the presence of the polyphenolic compounds, which could be explored further for the purpose of anticancer drug design.