The Effect of Curcumin Analogues on Metastasis Public
Williams, Ramone Faith (2010)
Published
Abstract
ABSTRACT The Effect of Curcumin Analogues on Metastasis By: Ramone Williams Tumors have often been referred to as "the wounds that never heal" because of the long suspected link between inflammation and cancer. In fact, preventable infections cause 15-20% of global cancer fatalities. The transcription factor and master regulator NF-kappaB is the "missing link" between these two processes. Furthermore the effective targeting of this "common denominator" provides the rationale for the potential of the use of age-old anti-inflammatory curcumin and its analogues as a potential antimetastatic agent. The purpose of this study was to examine the effect of novel curcumin analogues on the metastatic potential of cancer cells using a high-throughput image-based cell migration assay in a 96-well format. The high-throughput cell migration assay was developed by Platypus Technologies. The unique migration assay was utilized in conjunction with the ImageXpress5000 automated fluorescent microscope. The feasibility of the Oris™ Cell Migration Assay for the high-content screen was assessed and the imaging protocol and data analysis methods were optimized. 3,5-Bis(2-flourobenzylidene)piperidin-4-one (EF-24) and related analogs of curcumin were tested to assess their effect on the migratory potential of cancer cells and ranked based on their potent inhibitory capabilities. The effective inhibition of the migratory potential of cancer cells may lead to the development of a new generation of novel antimetastatic drugs. It has been found that the Oris™ Cell Migration Assay used in parallel with the IX5000 is a feasible methodology for the high-content screen. It was found that 60,000 cells/well and a 72 hour incubation-time for migration was optimal for the phenotypic image based assay. Surprisingly it was found that 20µM curcumin surfaced as the most potent drug when ranked based on its ability to inhibit migration in comparison to EF24 and AM- compounds.
Table of Contents
Table Of Contents Chapter 1: Introduction……………………………………………….……….……….1 Chapter 2: Materials And Methods………………………………….…………….….36 Chapter 3: Results And Figures…………………………………………………….…37 Chapter 4: Discussion…………………………………………………………………62 Chapter 5: Conclusion…………………………………………………………………74 References………………………………………………………………………………75 Appendix……………………………………………………………………….……….88
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