Aimed at developing accurate, reliable and cost-saving analytical techniques for drugs screening we
evaluated the potential of Fourier Transform (FT) InfraRed (IR) microspectroscopy (microFTIR) as
a quantitative pre-diagnostic approach for the rapid identification of IR signatures of drugs targeting
specific molecular pathways causing Chronic Myeloid Leukemia (CML). To obtain reproducible FTIR
absorbance spectra at the necessary spatial resolution we optimized sample preparation and acquisition
parameters on a single channel Mercury-Cadmium-Telluride (MCT) detector in the spectral interval of
frequencies from 4000 to 800 cm1. Single K562 cells were illuminated by Synchrotron Radiation (SR)
and a number of 15 K562 cells spread in monolayer were illuminated by a conventional IR source
(Globar), respectively. Combining IR spectral data with the results of complementary biochemical
investigations carried out in samples by different analytical methods we identified and cross-validated
IR signatures of drugs targeting the oncogenic protein BCR/ABL and its associated abnormal tyrosine
kinase activity in K562 cell line. Unsupervised pattern recognition performed by Hierarchical Cluster
Analysis (HCA) clustered the spectra of single K562 cells in two distinct groups roughly corresponding
to living and to apoptotic cells, respectively. The corresponding IR spectral profiles were assumed to
represent drug-resistant and drug-sensitive cells. Significant variations with increasing percentages of
apoptotic cells were observed after the treatment of K562 cells with drugs that directly or indirectly
target BCR/ABL. In conclusion, we suggest that microFTIR associated with multivariate data analysis
may be useful to assess drug compounds in ex vivo cancer cell models and possibly peripheral blast cells
from CML patients.
Product ID:
58243
Handle IRIS:
11562/345315
Deposited On:
March 30, 2012
Last Modified:
November 15, 2022
Bibliographic citation:
Bellisola, Giuseppe; DELLA PERUTA, Marco; Vezzalini, Marzia; Moratti, Elisabetta; Vaccari, L.; Birarda, G.; Piccinini, M.; Cinque, G.; Sorio, Claudio,
Tracking InfraRed signatures of drugs in cancer cells by Fourier Transform microspectroscopy«Analyst»
, vol. 135
, n. 12
, 2010
, pp. 3077-3086