Effect of Juice and Extracts from Saposhnikovia divaricata Root on the Colon Cancer Cells Caco-2.

Colorectal cancer ranks 3rd in terms of cancer incidence. Growth and development of colon cancer cells may be affected by juice and extracts from Saposhnikovia divaricata root. The objective of the research was to analyze the effect of S. divaricata juice and extracts on the viability, membrane integrity and types of cell death of Caco-2 cells. Juice and extracts were analyzed using Ultra-High Performance Liquid Chromatography-Mass Spectrometry (UHPLC-MS) and in respect of the presence of antioxidants, total carbohydrates, protein, fat and polyphenols. The contents of cimifugin ß-D-glucopyranoside, cimifugin, 4'-O-glucopyranosyl-5-O-methylvisamminol, imperatorin and protein were the highest in juice. 50% Hydroethanolic extract had the greatest antioxidant potential, concentration of polyphenols and fat. Water extract was characterized by the highest content of glutathione. Juice and 75% hydroethanolic extract contained the most carbohydrates. After the application of juice, 50% extract and the juice fraction containing the molecules with molecular weights >50 kDa, a decrease of the cell viability was noted. Juice and this extract exhibited the protective properties in relation to the cell membranes and they induced apoptosis. The knowledge of further mechanisms of anticancer activity of the examined products will allow to consider their use as part of combination therapy.

Nanostructures of diamond, graphene oxide and graphite inhibit CYP1A2, CYP2D6 and CYP3A4 enzymes and downregulate their genes in liver cells.

INTRODUCTION AND OBJECTIVE: Currently, carbon nanostructures are vastly explored materials with potential for future employment in biomedicine. The possibility of employment of diamond nanoparticles (DN), graphene oxide (GO) or graphite nanoparticles (GN) for in vivo applications raises a question of their safety. Even though they do not induce a direct toxic effect, due to their unique properties, they can still interact with molecular pathways. The objective of this study was to assess if DN, GO and GN affect three isoforms of cytochrome P450 (CYP) enzymes, namely, CYP1A2, CYP2D6 and CYP3A4, expressed in the liver. METHODS: Dose-dependent effect of the DN, GO and GN nanostructures on the catalytic activity of CYPs was examined using microsome-based model. Cytotoxicity of DN, GO and GN, as well as the influence of the nanostructures on mRNA expression of CYP genes and CYP-associated receptor genes were studied in vitro using HepG2 and HepaRG cell lines. RESULTS: All three nanostructures interacted with the CYP enzymes and inhibited their catalytic activity in microsomal-based models. CYP gene expression at the mRNA level was also downregulated in HepG2 and HepaRG cell lines. Among the three nanostructures, GO showed the most significant influence on the enzymes, while DN was the most inert. CONCLUSION: Our findings revealed that DN, GO and GN might interfere with xenobiotic and drug metabolism in the liver by interactions with CYP isoenzymes responsible for the process. Such results should be considered if DN, GO and GN are used in medical applications.