Anticancer Studies Of Ximenia Americana And Catharanthus Roseus In Human Breast Cancer Cell Lines Mcf7 And Mda-Mb-231
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Date
2021-03
Authors
Eltahir, Nagla Mustafa Eltayeb
Journal Title
Journal ISSN
Volume Title
Publisher
Universiti Sains Malaysia
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
Description
Keywords
Cancer