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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