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Identifying the Responses from the Estrogen Receptor-Expressed MCF7 Cells Treated in Anticancer Drugs of Different Modes of Action Using Live-Cell FTIR Spectroscopy
journal contribution
posted on 2020-05-23, 00:13 authored by Ali Altharawi, Khondaker Miraz Rahman, Ka Lung Andrew ChanRecently, we have shown that changes
in Fourier transform infrared
(FTIR) spectra of living MDA-MB-231 cells (a triple negative cell
line) upon exposure to anticancer drugs reflect the changes in the
cellular compositions which are correlated to the modes of action
of drugs. In the present study, MCF7 cells (an estrogen receptor expressing
breast cancer cell line) were exposed to three anticancer drugs belonging
to two well-characterized anticancer classes: selective estrogen receptor
modulators (SERMs) and DNA-intercalating agent. First, we evaluated
if the changes in the spectrum of cells are according to the modes
of action of drugs and the characteristics of the MCF7 cell line in
the same way as the MDA-MB-231 cell. Living MCF7 cells were treated
in the three drugs at half maximal inhibitory concentration (IC50),
and the difference spectra were analyzed using principal component
analysis (PCA). The results demonstrated clear separation between
tamoxifen/toremifene (SERM)-treated cells from the doxorubicin (DNA-intercalator)-treated
and untreated cells (control). Tamoxifen and toremifene induced similar
spectral changes in the cellular compositions of MCF7 cells and lead
to the clustering of these two drugs in the same quadrant of the principal
component 1 (PC1) versus PC2 score plots. The separation is mostly
attributed to their similar modes of actions. However, doxorubicin-treated
MCF7 cells highlighted spectral changes that mainly occur in bands
at 1085 and 1200–1240 cm–1, which could be
associated with the DNA-intercalation effects of the drug. Second,
the pairwise PCA at various individual time points was employed to
investigate whether the spectral changes of MCF7 and MDA-MB-231 cells
in response to the IC50 of tamoxifen/toremifene and doxorubicin are
dependent on the characteristics of the cell lines. The estrogen-expressing
MCF7 cells demonstrated significant differences in response to the
SERMs in comparison to the triple negative MDA-MB-231 cells, suggesting
that different modes of action have taken place in the two tested
cell lines. In contrast, the doxorubicin-treated MDA-MB-231 and MCF7
cells show similar changes in 1150–950 cm–1, which indicates that the DNA intercalation effect of doxorubicin
is found in both cell lines. The results have demonstrated that live-cell
FTIR analysis is sensitive to the different modes of action from the
same drugs on cells with different characteristics.
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Keywords
well-characterized anticancer classesbreast cancer cell lineMDA-MB -231 cellcell linesLiving MCF 7 cellsPCASERMdoxorubicin-treated MCF 7 cellsdoxorubicin-treated MDA-MB -231Estrogen Receptor-Expressed MCF 7 Cells TreatedMCF 7 cellsDNA intercalation effectanticancer drugsMCF 7 cells showestrogen-expressing MCF 7 cellslive-cell FTIR analysisPC 2 score plotsMCF 7 cell lineLive-Cell FTIR SpectroscopyICMDA-MB -231 cellsestrogen receptor modulators
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