Characterising cytotoxic agent action as a function of the cell cycle using fourier transform infrared microspectroscopy

Abstract

Fourier Transform Infrared (FTIR) micro-spectroscopy measurements were acquired to study infrared signatures of chemotherapeutic response as a function of the cell cycle. Renal carcinoma Caki-2 cells were exposed to IC50 doses of 5-fluorouracil and Paclitaxel for a period of 24 hours. The inherent cell cycle infrared signatures from untreated and drug-treated cells were successfully retrieved by the construction of a robust SVM able to discriminate the cell cycle phases of this cell line with an average accuracy of 83.7%. The overriding infrared signature observed relates to an apoptotic biochemical response that does not appear to be correlated with the events affected by the drugs' mode of action or the cell cycle. Since apoptosis is a well conserved mechanism among living species, these results suggest that both the stages of proliferation as well as the absence/presence of apoptosis need to be taken into account in order to elucidate the fine biochemical details revealing the immediate cellular response to the drug in order to assign reliable spectral patterns of drug action.

Probing the action of a novel anti-leukaemic drug therapy at the single cell level using modern vibrational spectroscopy techniques

“…Here, the major DNA peaks have been explored to assess if one of the targets of BaP could in fact be DNA and to confirm that what was being monitored in this study was not simply cell death. One of the vibrations as a marker for the latter hypothesis is the carbonyl vibration for protein linking in the amide I band at 1657 cm −1 which has been reported to significantly decrease with apoptosis 48 . A visual inspection of the spectra in Fig.…”

Chemotherapeutic response to cisplatin-like drugs in human breast cancer cells probed by vibrational microspectroscopy

“…This constitutes an unmatched approach for routine chemical proling of cells, allowing accurate examination of cellular environments and monitoring of drug bioavailability, biodistribution and target site accumulation aer administration, as well as drug delivery across biological barriers and cellular response to treatment. [30][31][32] Since cells are known to have specic vibrational spectroscopic signatures for different physiological conditions (regarding viability, cell cycle, apoptosis or stress), a correlation between a particular vibrational prole and a denite effect or mode of action should predictably be attained.…”

Can mid-infrared biomedical spectroscopy of cells, fluids and tissue aid improvements in cancer survival? A patient paradigm

“…47 They were able to follow progression during chemotherapy largely based on lipid IR absorptions, which have been demonstrated as a spectral marker of apoptosis. 48,49 They were unable to predict the treatment outcomes based on the PBMC spectra obtained in pre-treatment days, however, it was shown that FTIR spectroscopy could provide additional information on chemotherapeutic response of an individual patient basis; an application that may be vital to identify unexpected complications in real time as soon as they may appear during treatment.…”