Anticancer Studies Of Ximenia Americana And Catharanthus Roseus In Human Breast Cancer Cell Lines Mcf7 And Mda-Mb-231
| dc.contributor.author | Eltahir, Nagla Mustafa Eltayeb | |
| dc.date.accessioned | 2022-04-05T00:05:58Z | |
| dc.date.available | 2022-04-05T00:05:58Z | |
| dc.date.issued | 2021-03 | |
| dc.description.abstract | Ximenia americana is a medicinal plant found in most African countries. It has been used traditionally to treat numerous diseases, including cancer. This study aimed to investigate the antiproliferative effect of X. americana leaves extract and fractions against breast cancer cell lines, determine the mechanisms of action and identify the major bioactive principle (s) in the most active fraction. Bioassay-guided fractionation of X. americana leaves using repeated open column chromatography and MTT assay resulted in the separation of SFr.6.2 as the most active subfraction with antiproliferative effect against MCF7 and MDA-MB-231 cell lines. SFr.6.2 showed dose- and time-dependent antiproliferative effect against both cell lines with more selectivity towards MCF7 cells. Moreover, the antiproliferative effect of SFr.6.2 on MCF7 was more significant than the standard drug tamoxifen. The IC50 values of SFr.6.2 and tamoxifen on MCF7 cells were 3.02 ± 0.21 and 5.97 ± 0.54 μg/ml, respectively. SFr.6.2 exerted less potency on non-tumourigenic cell line MCF 10A with a selectivity index of 3.14 compared to 1.64 for tamoxifen. Using flow cytometry analysis, SFr.6.2 showed dose-dependent cell cycle arrest at G2/M phase and apoptosis induction on MCF7 cells. SFr.6.2 chemical constituents were further analysed by LCMS-Q-TOF. The obtained chromatogram demonstrates the presence of valuable bioactive compounds which could be responsible for the anticancer activity of SFr.6.2. In addition to that, the chromatographic separation of X. americana leaves extract yielded three compounds, lupeol (1), daucosterol (2) and avicularin (3). This study reported the separation and identification of bioactive compounds from X. americana leaves with potent and selective antiproliferative effect against MCF7 cell line. The antiproliferative effect of the separated compounds was mediated through arresting G2/M phase and apoptosis induction. To the best of our knowledge, this is the first report of the isolation of daucosterol from Ximenia genus. The study also investigated the anti-migratory and anti-invasive effect of Catharanthus roseus methanolic extract on highly aggressive triple-negative breast cancer (TNBC) cell line, MDA-MB-231 and determined the molecular mechanisms of action. C. roseus extract significantly inhibited the migration and invasion of MDA-MB-231 cells at non-cytotoxic concentrations in scratch and Transwell assays. ELISA and gelatin zymography showed that the extract decreased the secretions and activities of MMP2 and MMP9 in a dose-dependent manner. The effect of C. roseus extract in the expression of 84 genes commonly involved in cell motility was assessed using Human Cell Motility RT2 Profiler PCR Array and Real time-PCR (RT-PCR). Treatment of MDA-MB-231 cells by C. roseus extract at 4 μg/ml for 24 h resulted in significant downregulation of 52 genes. These genes are mainly involved in extracellular matrix degradation, cytoskeleton reorganization, focal adhesions and invadopodia formation. Gene ontology (GO) and Kyoto Encyclopedia of Genes and Genomes (KEGG) pathway analysis showed that the downregulated genes are enriched in biological processes and pathways closely related to cell motility. This study suggests that C. roseus extract inhibits migration and invasion of MDA-MB-231 cells via downregulation of the expression of various genes implicated in several motility cellular events. The extract may contain compound (s) that could synergistically inhibit the expression of critical therapeutic targets which could be explored further for future breast cancer treatment. In conclusion, this study provided data about the therapeutic potential of X. americana | en_US |
| dc.identifier.uri | http://hdl.handle.net/123456789/15032 | |
| dc.language.iso | en | en_US |
| dc.publisher | Universiti Sains Malaysia | en_US |
| dc.subject | Cancer | en_US |
| dc.title | Anticancer Studies Of Ximenia Americana And Catharanthus Roseus In Human Breast Cancer Cell Lines Mcf7 And Mda-Mb-231 | en_US |
| dc.type | Thesis | en_US |
Files
License bundle
1 - 1 of 1
Loading...
- Name:
- license.txt
- Size:
- 1.71 KB
- Format:
- Item-specific license agreed upon to submission
- Description: