Studies of the Anti-Cancer Effects of Flavokawin B Onhuman Breast Cancer Cell Lines, Mcf7 And Mda-Mb-231
A natural compound, Flavokawin B, isolated and purified from extract of Alpinia zerumbet was investigated for its anti-cancer properties on breast cancer cell lines, estrogen dependant MCF-7 and estrogen non-dependant MDA-MB-23. Tamoxifen, a non-steroidal anti-estrogen, primarily exploited as a...
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| Format: | Thesis |
| Language: | English English |
| Published: |
2005
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| Subjects: | |
| Online Access: | http://psasir.upm.edu.my/id/eprint/6331/1/FPSK%28M%29_2005_9.pdf |
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| Summary: | A natural compound, Flavokawin B, isolated and purified from extract of
Alpinia zerumbet was investigated for its anti-cancer properties on breast
cancer cell lines, estrogen dependant MCF-7 and estrogen non-dependant
MDA-MB-23. Tamoxifen, a non-steroidal anti-estrogen, primarily exploited
as a drug against hormone-dependent breast cancer, acts as the positive
control for this study. MCF-IOA, mammary epithelial cells serve as the
negative control. The cytotoxicities of Flavokawin B and Tamoxifen on
human breast cells were investigated using the MTT assay. The results
showed that the ICSo @ S.E.M) value of Flavokawin B on MCF-7 cell line
was determined to be 1 1.5 Ifi 0.01 5 pM/ml whilst the ICSo with Tarnoxifen
was at 10.2 + 0.012 W m l . The ICS0 value of Flavokawin B on MDA-MB-
23 1 cell line was determined to be 17.5 + 0.0 19 pM/ml whilst the ICS0 value
of Tamoxifen was at 32.5 2 4.2 pM/ml. The MTT assay results on normal
epithelial cell line, MCF-1 OA treated with Flavokawin B demonstrated that
the ICS0 value was 38.0 0.032 pM/ml whereas MCF-1OA treated with
Tamoxifen had an ICSo value of 28 + 0.021 pM/ml. All values were
statistically significant (p<0.05), as analysed using one sample T-test. The
breast cancer cell lines treated at ICS0 concentration of both compounds
before proceeding using confocal microscopy. There were no significant
changes observed in the untreated cells. However, apoptotic features were
that include membrane blebbing and nucleus condensation were evident at
24 hours. At 48 and 72 hours post treatment, convolution of nuclear
membrane, destruction of nuclear membrane and fragmentation of the
nucleus were observed. The TUNEL assay is designed to specifically detect
and quantify apoptotic cells within a cell population, which primarily
consists of both apoptotic and non-apoptotic cells. The TUNEL assay
conducted showed that Flavokawin B induces more apoptosis on MCF-7
and MDA-MB-23 1 compared to Tamoxifen. In contrast, Flavokawin B has
lesser lethal effects on MCF-1OA as compared to Tamoxifen. The levels of
IL-6 secretion in MDA-MB-231 cell line decreased significantly after
treatment with Flavokawin B. Immunofluorescence studies demonstrated
that the levels of IL-6 secretion commensurate with the presence of
membrane bound IL-6r when proliferation of the breast cells was inhibited
during treatment with both the compounds. The MCF-7 and MDA-MB-23 1
cell lines were arrested at G1 phase when treated with both Flavokawin B
and Tamoxifen. This shows that both the treatment follows similar
mechanism to induce cell phase arrest. In conclusion, it could be confirmed
that the pure compound Flavokawin B induces apoptosis in MCF-7 and
MDA-MB-23 1 breast cancer cell lines contributing to the discovery of new
alternative treatment strategy for breast cancer. |
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