Towards identifying the mode of action of drugs using live-cell FTIR spectroscopy

Altharawi, Ali; Rahman, Khondaker Miraz; Chan, K. L. Andrew

doi:10.1039/c8an02218f

Cited by 22 publications

(24 citation statements)

References 64 publications

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“…A significant decrease was observed, in the bands related to the stretching of O-P-O and C-O at 1080 cm −1 and 1050 cm −1 , respectively. Those spectral changes are related to changes in the DNA-phosphate backbone, because of the DNA disintegrating effect of doxorubicin [121].…”

Section: Dna Damage At the Cellular Levelmentioning

confidence: 99%

Molecular Spectroscopic Markers of DNA Damage

Sofińska¹,

Wilkosz²,

Szymoński³

et al. 2020

Molecules

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Every cell in a living organism is constantly exposed to physical and chemical factors which damage the molecular structure of proteins, lipids, and nucleic acids. Cellular DNA lesions are the most dangerous because the genetic information, critical for the identity and function of each eukaryotic cell, is stored in the DNA. In this review, we describe spectroscopic markers of DNA damage, which can be detected by infrared, Raman, surface-enhanced Raman, and tip-enhanced Raman spectroscopies, using data acquired from DNA solutions and mammalian cells. Various physical and chemical DNA damaging factors are taken into consideration, including ionizing and non-ionizing radiation, chemicals, and chemotherapeutic compounds. All major spectral markers of DNA damage are presented in several tables, to give the reader a possibility of fast identification of the spectral signature related to a particular type of DNA damage.

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Section: Dna Damage At the Cellular Levelmentioning

confidence: 99%

Molecular Spectroscopic Markers of DNA Damage

Sofińska¹,

Wilkosz²,

Szymoński³

et al. 2020

Molecules

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“…We have recently shown that ATR FTIR spectroscopy combined with principal component analysis (PCA) is a powerful technique to distinguish the response of MDA-MB-231 cells, a triple negative cell, based on their different modes of actions. The results have shown that drugs with the same mode of action (tamoxifen and toremifene) were clustered together and well-separated from other drugs of different modes of action (imatinib and doxorubicin) …”

Section: Introductionmentioning

confidence: 99%

Identifying the Responses from the Estrogen Receptor-Expressed MCF7 Cells Treated in Anticancer Drugs of Different Modes of Action Using Live-Cell FTIR Spectroscopy

2020

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Recently, 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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“…Traditionally, the band at 1087 cm −1 was used instead to map the nucleus of cells based on the ν sym (PO 2 ) – in the DNA backbone because it is a stronger band. However, using the band at 1714 cm −1 to map the distribution of the DNA is more specific than the 1087 cm −1 band as other non-nucleus specific biocomponents such as RNA, phospholipid, phosphorylated protein, 35 and other phosphate containing metabolites such as adenosine triphosphate and adenosine diphosphate can contribute to the absorbance in that region. As a result, images generated from the integrated absorbance within the 1102–1065 cm −1 spectral range (Figs.…”

Section: Resultsmentioning

confidence: 99%

Transmission Fourier Transform Infrared Spectroscopic Imaging, Mapping, and Synchrotron Scanning Microscopy with Zinc Sulfide Hemispheres on Living Mammalian Cells at Sub-Cellular Resolution

et al. 2020

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Fourier transform infrared (FT-IR) spectroscopic imaging and microscopy of single living cells are established label-free technique for the study of cell biology. The constant driver to improve the spatial resolution of the technique is due to the diffraction limit given by infrared (IR) wavelength making subcellular study challenging. Recently, we have reported, with the use of a prototype zinc sulfide (ZnS) transmission cell made of two hemispheres, that the spatial resolution is improved by the factor of the refractive index of ZnS, achieving a λ/2.7 spatial resolution using the synchrotron–IR microscopy with a 36× objective with numerical aperture of 0.5. To refine and to demonstrate that the ZnS hemisphere transmission device can be translated to standard bench-top FT-IR imaging systems, we have, in this work, modified the device to achieve a more precise path length, which has improved the spectral quality of the living cells, and showed for the first time that the device can be applied to study live cells with three different bench-top FT-IR imaging systems. We applied focal plane array (FPA) imaging, linear array, and a synchrotron radiation single-point scanning method and demonstrated that in all cases, subcellular details of individual living cells can be obtained. Results have shown that imaging with the FPA detector can measure the largest area in a given time, while measurements from the scanning methods produced a smoother image. Synchrotron radiation single-point mapping produced the best quality image and has the flexibility to introduce over sampling to produce images of cells with great details, but it is time consuming in scanning mode. In summary, this work has demonstrated that the ZnS hemispheres can be applied in all three spectroscopic approaches to improve the spatial resolution without any modification to the existing microscopes.

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Towards identifying the mode of action of drugs using live-cell FTIR spectroscopy

Abstract: Fourier transform infrared spectroscopy (FTIR) has been shown to be a promising tool for identifying the mode of action of drugs.

Cited by 22 publications

References 64 publications

Molecular Spectroscopic Markers of DNA Damage

Molecular Spectroscopic Markers of DNA Damage

Identifying the Responses from the Estrogen Receptor-Expressed MCF7 Cells Treated in Anticancer Drugs of Different Modes of Action Using Live-Cell FTIR Spectroscopy

Transmission Fourier Transform Infrared Spectroscopic Imaging, Mapping, and Synchrotron Scanning Microscopy with Zinc Sulfide Hemispheres on Living Mammalian Cells at Sub-Cellular Resolution

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