Effects of Gracilaria Changii Extract Onapoptosis snd Gene Expression of Mcf-7and Mda-Mb-23 1 Breast Cancer Cell Lines
Cancer is a large group of diseases characterized by uncontrolled growth and spread of abnormal cells. Hundreds of research studies have demonstrated significant benefit of the use of natural products in the treatment of cancer and scientists believe examining new natural products will continue t...
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| Format: | Thesis |
| Language: | English English |
| Published: |
2006
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| Online Access: | http://psasir.upm.edu.my/id/eprint/6404/1/FPSK%28M%29_2006_10.pdf http://psasir.upm.edu.my/id/eprint/6404/ |
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| Summary: | Cancer is a large group of diseases characterized by uncontrolled growth and spread of
abnormal cells. Hundreds of research studies have demonstrated significant benefit of the
use of natural products in the treatment of cancer and scientists believe examining new
natural products will continue to turn up even more useful drugs to treat cancer. Marine
organisms are a rich source for natural products and many compounds that are derived
from these have generated interest for their cytotoxicities. Gracilaria changii is a type of
red seaweed which comes from the family Rhodophyta. It is a relatively abundant
seaweed in Malaysia can be found in the mangrove areas. In this study, the
chemotherapeutic potential of Gracilaria changii in selected reproductive cancer cell
lines was evaluated together with tamoxifen, a commercially used drug in cancer
treatment. Exposure of breast, ovarian and cervical cancer cell lines, to a range of
Gracilaria changii extracts demonstrated growth inhibition in some of these cancer cells
in a dose-dependent manner. The Gracilaria changii extracts received from Kolej
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Universiti Sains dan Teknologi Malaysia (KUSTEM) were methanol, buthanol and
diethyl ether extracts. The methanol extract gave the most promising ICso values, as
determined by the 3-(4,5-dimethylthiazol-2-yl)-2,5-diphenyltetrazolium bromide (MTT)
reduction assay and the results are as follows: MCF-7 (7.8 pglml), MDA-MB-23 1 (25
pglml) HeLa (70.26 pglml) and Caov-3 (90.46 pglml). Since the results for the breast
cancer cell lines were significant compared to the ovarian and ceivical cancer cell lines,
they were chosen for further analysis. The normal breast cell line, MCF-1OA was also
tested and the ICjo value was found to be > 1000 pglml, indicating that the methanol
extract was not cytotoxic to normal cells. AOPI staining was used to study the
morphology of the cells treated with the extract. Apoptotic features that included
membrane blebbing and nucleus condensation were evident in MCF-7 and MDA-MB-
23 1 cancer cells. Subsequently, the TUNEL assay was conducted to determine and
quantitate the apoptotic cells within a cell population. The results suggest that the
methanol extract was better of inducing cell death by stimulating apoptosis than
tamoxifen. This is based on the significantly higher percentage of apoptotic cells in the
G.cl7utzgii methanol extract treated cancer cells as compared to tamoxifen. For MCF-7
and MDA-MB-23 1 cell lines, p was <0.01 when compared with control (24 hours) and P
of <0.001 when compared with control for 48 hours. In addition, gene expression analysis
was performed using the microarray technology. This technology which allows the
simultaneous analysis of a large number of nucleic acid hybridization experiments and
was cal~iedo ut to determine the gene expression profile. Preliminary work on micorarray
was conducted using MCF-7 cell line only, due to time constraints and limited funding.
Upon treatment with the methanol extract on MCF-7, several suppressed genes were
identified including haplotype nlb mitochondrion complete genome, melanomaassociated
antigen p97 isofonn 1 and damage-specific DNA binding protein 2 (ddb2).
The results showed that the three genes regulated by the methanol extract encode proteins .
that belongs to DNA repair, protection against membrane-lipid peroxidation and maternal
inheritance family, which may play an important role for the cancer treatment. It was
hrther confirmed using Reverse Transcription Polymerase Chain Reaction (RT-PCR).
Therefore, the methanol extract of Gracilaria chaizgii is a potential candidate to be
d-ev eloped as a chemotherapeutic agent in the treatment of estrogen receptor-positive
breast cancer |
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