Laboratory of Biophysics, Intercollegiate Faculty of Biotechnology University of Gdansk and Medical University of Gdansk, Abrahama 58, 80-307 Gdańsk, Poland
Prof. Jacek Piosik
Laboratory of Biophysics, Intercollegiate Faculty of Biotechnology University of Gdansk and Medical University of Gdansk, Abrahama 58, 80-307 Gdańsk, Poland
We formulated and analyzed a novel nanoformulation of the anticancer drug cisplatin (Cis) with C60 fullerene (C60+Cis complex) and showed its higher toxicity toward tumor cell lines in vitro when compared to Cis alone. The highest toxicity of the complex was observed in HL-60/adr and HL-60/vinc chemotherapy-resistant human leukemia cell sublines (resistant to Adriamycin and Vinculin, respectively). We discovered that the action of the C60+Cis complex is associated with overcoming the drug resistance of the tumor cell lines through observing an increased number of apoptotic cells in the Annexin V/PI assay. Moreover, in vivo assays with Lewis lung carcinoma (LLC) C57BL/6J male mice showed that the C60+Cis complex increases tumor growth inhibition, when compared to Cis or C60 fullerenes alone. Simultaneously, we conducted a molecular docking study and performed an Ames test. Molecular docking specifies the capability of a C60 fullerene to form van der Waals interactions with potential binding sites on P-glycoprotein (P-gp), multidrug resistance protein 1 (MRP-1), and multidrug resistance protein 2 (MRP-2) molecules. The observed phenomenon revealed a possible mechanism to bypass tumor cell drug resistance by the C60+Cis complex. Additionally, the results of the Ames test show that the formation of such a complex diminishes the Cis mutagenic activity and may reduce the probability of secondary neoplasm formation. In conclusion, the C60+Cis complex effectively induced tumor cell death in vitro and inhibited tumor growth in vivo, overcoming drug resistance likely by the potential of the C60 fullerene to interact with P-gp, MRP-1, and MRP-2 molecules. Thus, the C60+Cis complex might be a potential novel chemotherapy modification.
The objective of the present study was to evaluate the antibacterial properties of a plant secondary metabolite - caffeine. Caffeine is present in over 100 plant species. Antibacterial activity of caffeine was examined against the following plant-pathogenic bacteria: Ralstonia solanacearum (Rsol), Clavibacter michiganesis subsp. sepedonicus (Cms), Dickeya solani (Dsol), Pectobacterium atrosepticum (Pba), Pectobacterium carotovorum subsp. carotovorum (Pcc), Pseudomonas syringae pv. tomato (Pst), and Xanthomonas campestris subsp. campestris (Xcc). MIC and MBC values ranged from 5 to 20 mM and from 43 to 100 mM, respectively. Caffeine increased the bacterial generation time of all tested species and caused changes in cell morphology. The influence of caffeine on the synthesis of DNA, RNA and proteins was investigated in cultures of plant pathogenic bacteria with labelled precursors: [(3)H]thymidine, [(3)H]uridine or (14)C leucine, respectively. RNA biosynthesis was more affected than DNA or protein biosynthesis in bacterial cells treated with caffeine. Treatment of Pba with caffeine for 336 h did not induce resistance to this compound. Caffeine application reduced disease symptoms caused by Dsol on chicory leaves, potato slices, and whole potato tubers. The data presented indicate caffeine as a potential tool for the control of diseases caused by plant-pathogenic bacteria, especially under storage conditions.
Among metal-based nanoparticles, silver nanoparticles (AgNPs) are particularly appealing because of their stability, functionality, and documented antimicrobial properties. AgNPs also offer the possibility of different surface modifications. In this work, we functionalized AgNPs with thiobarbituric acid or 11-mercaptoundecanoic acid residues to improve the nanoparticles’ biological activities. Subsequently, we assessed the physicochemical properties of newly synthesized AgNPs using a wide range of biophysical methodologies, including UV/vis and fluorescence spectroscopy, atomic force and scanning electron microscopy, and dynamic light scattering and isothermal titration calorimetry. Next, we examined the effect of nanoparticles functionalization on AgNPs mutagenicity and toxicity. Our study revealed that AgNPs’ surface modification affects nanoparticles aggregation, and also impacts nanoparticles’ interaction with model acridine mutagen ICR-191. AgNPs coated with MUA showed the most interesting interactions with tested ICR-191, slightly modulating its toxicity properties by decreasing the viability in treated cells.