Akademik Veri Yönetim Sistemi
EUROPEAN JOURNAL OF PHARMACEUTICAL SCIENCES, cilt.123, ss.377-386, 2018 (SCI-Expanded)
Cyclodextrins (CD) are natural macrocyclic oligosaccharides linked by alpha(1,4) glycosidic bonds. Hydrophobic cavity of CDs are able to incorporate small molecules, ions, macromolecules which makes them excellent delegates for forming nanoparticulate carriers upon chemical modification to render amphiphilicity to CDs. In this study, blank 6OCapro beta CD nanoparticle was prepared and administered to MCF-7 breast cancer cells. The effects of these nanoparticles on the cells were investigated in depth through biochemical and proteomic tests following 48 h of incubation. Proteomics studies revealed that apoptosis-related protein levels of hnRNP and CBX1 were increased while HDGF was not affected supporting the idea that 6OCapro beta CD nanoparticles prevent cell proliferation. Gene expression studies were generally in correlation with protein levels since gene expression was significantly stimulated while protein levels were lower compared to the control group suggesting that a post-transcriptional modification must have occurred. Furthermore, 6OCapro beta CD was observed to not trigger multidrug resistance as proved with RT-PCR that effectuates another exquisite characteristic of 6OCapro beta CD nanoparticle as carrier of chemotherapeutic drugs. Metabolomic pathways of CD effect on MCF7 cells were elucidated with HMDB as serine biosynthesis, transmembrane transport of small molecules, metabolism of steroid hormones, estrogen biosynthesis and phospholipid biosynthesis. In conclusion, 6OCapro beta CD is a promising nanoparticulate carrier for chemotherapeutic drugs with intrinsic apoptotic effect to be employed in treatment of breast cancer and further studies should be conducted in order to comprehend the exact mechanism of action.