ABSTRACT
MICROARRAY APPLICATIONS FOR DETERMINATION OF THE EFFECTS OF EMODIN
ON BREAST CANCER CELL LINES
Ekenel Qomi, Emilia
M.S., Department of Biotechnology
Supervisor: Prof. Dr. Mesude Iscan
Co-Supervisor: Assoc. Prof. Dr. Nursen Ç / oruh
February 2012, 191 pages
Cancer is a genetic disease that is characterized by uncontrolled cells growth. Breast
cancer is a type of cancer originating from breast tissue. Some breast cancers are
sensitive to hormones such as estrogen which makes it possible to treat them by
blocking the effects of these hormones in the target tissues. These require less
aggressive treatment than hormone negative cancers. Breast cancers without
hormone receptors, are higher-risk, and are treated more aggressively.
The aim of our study is to investigate the effect of emodin on MCF-7 which is ER
(estrogen receptor) positive, and MDA-MB-231 (ER negative) cancerous cell lines.
Emodin which is a phytoestrogen component, extracted from rheum (genus) plant,
has been reported to suppress the growth of tumor in some clinical situation, and
it&rsquo / s found that emodin induced apoptosis through the decrease of Bcl-2/Bax ratio
and the increase of cytoplasm cytochrome c concentration in human breast cancer
Bcap-37 cells. Comparing the effect of emodin between ER positive and ER negative
cells at the molecular level was investigated by Microarray analysis of gene
expressions using Affymetrix Human Genome U133 plus 2.0 Array. The microarray
data analysis was performed by using BRB-Array Tools, v.4.2.0.
GST and its classes / Alpha, Mu, Pi, Theta, Sigma, Omega, Zeta and Kappa is our
interested genes because of its role in regulating susceptibility to cancer, by their
ability to metabolize reactive electrophilic intermediates to usually less reactive and
more water soluble glutathione conjugates. And also its have a role in detoxifying
the damage caused by oxidative stress which is a result of the radiotherapy.
v
The differentially expressed genes from emodin treated and untreated control
breast cancer cell lines were compared after normalization and filtering and
annotated, it was shown that the top 10 highly (significantly) varied genes belong to
the biological processes such as (namely) cell cycle, cell division, cell proliferation,
mitosis and meiosis, this insure the relation of emodin to the cell growth processes
in the cancerous cells. The analysis of the change on the cell growth confirmed the
anti-tumor effect of emodin.
About the effect of emodin treatment on MCF-7 and MDA-MB-231 cancerous cell
lines separately / Both cells its significant genes was belong to cell growth biological
processes, in MCF-7 cells in-addition other biological processes was shown, for
example / stimulus to estradoil response, and the metabolism of xenobiotic by
cytochrome p450, so CYP1A1 gene code for a protein which is used in emodin
metabolism. The varied gene number was nearly 4400 gene from the scatter plot
result in MCF-7 cells while in MDA-MB-231 cells it was nearly 3400 gene, these
result insured the effect of emodin as a phytoestrogenic component as MCF-7 cells
are ER positive cells, so emodin bind to the ER in MCF-7 cells and affected more
gene number than MDA-MB-231.
More number of GST enzyme classes changed in MCF-7 cells than MDA-MB-231,
and the effect of emodin as anti-cancer showed different change of GST genes
between MCF-7 and MDA-MB-231.
The results confirmed by network analysis done, to find the most related genes to
our top 10 regulated gene list, and these genes were analyzed / most of them where
in our gene list, and their regulation after emodin treatment analyzed and the result
was supported to emodin as anti-tumor and phytoestrogenic component.
| Identifer | oai:union.ndltd.org:METU/oai:etd.lib.metu.edu.tr:http://etd.lib.metu.edu.tr/upload/12614200/index.pdf |
| Date | 01 March 2011 |
| Creators | Qomi Ekenel, Emilia |
| Contributors | Iscan, Prof. Dr. Mesude |
| Publisher | METU |
| Source Sets | Middle East Technical Univ. |
| Language | English |
| Detected Language | English |
| Type | M.S. Thesis |
| Format | text/pdf |
| Rights | Access forbidden for 1 year |
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