ABSTRACT
Cancer is considered as a challenging deathly disease and discovering or synthesis of new cytotoxic agents is a worldwide attempt. In this study, a group of recently synthesized chalcones, with the structure of 1,3-diarylprop-2-en-1-one having differesnt COX-1 and/or COX-2 selectivities, have been examined on human hepatocarcinoma [HepG2], lung carcinoma [A549], and breast adenocarcinoma [MCF-7] cell line, using Sulforhodamine B [SRB] assay. Briefly, cells were treated with 1-100 microM of each compound for 72, 96 and 168 hours. In each case, a control row was set with the exposure of cells to compounds-free solvents. Median lethal concentration [LC50] values [compared to controls] were calculated using regression fitness analysis on GraphPad Prism® software. Our results show that the subgroup possessing p-azido COX-2 pharmacophore seems to be more cytotoxic, while the cells seem to show more acquired resistance to them and the subgroup possessing a p-MeSO2NH COX-2 pharmacophore is less cytotoxic, while the cells also acquire less resistance to them. In conclusion, considering the diversity in COX-1 or COX-2 inhibition among these compounds in each group, and also revealing no correlation between COX inhibition selectivity and cell death, it seems that selective inhibition of each isoenzyme doesn't cause substantial effect on toxicity potency. Further studies to determine the main mechanism[s] for these compounds induced cell death are encouraged
ABSTRACT
The current methods for treatment of cancers are inadequate and more specific methods such as gene therapy are in progress. Among different vehicles, cationic liposomes are frequently used for delivery of genetic material. This investigation aims to prepare and optimize DOTAP cationic liposomes containing an antisense oligonuclotide [AsODN] against protein kinase C alpha in non-small cells lung cancer [NSCLC]
To perform this investigation, two different methods of ethanol injection and thin film hydration were used to prepare AsODN-loaded DOTAP liposomes
The formulated liposomes were then evaluated for their morphology, particle size, zeta potential and encapsulation efficiency, and the best formulation was chosen. In-vitro growth inhibitory effect of encapsulated ODN on A549 cells were evaluated by MTT and colonogenic assay. The physical and serum stability of liposomal ODN were also evaluated
Thin film hydration method resulted in large liposomes that required downsizing by extrusion with an encapsulation efficiency of 13%. Ethanol injection, in a single step gave liposomes with a small size of 115 nm and an encapsulation efficiency of around 90% which were physically stable for 6 months. The optimized liposome could protect oligonucleotides from degradation by nuclease. Cell studies showed a 20% sequence-specific inhibition of cell growth in MTT assay and revealed an LC[50] of 103 nM in colonogenic studies
In conclusion, ethanol injection was able to provide suitable liposomes from the permanently charged DOTAP. Also the resulted liposomes were able to inhibit the growth of lung cancer cells