Microsoft powerpoint - poster biowin aderenne_format coupé.pptx

The FTIR spectrum of prostate cancer cells signs the mode of action
The FTIR spectrum of prostate cancer cells si
of anticancer drugs
gns the mode of action
Allison Derenne, Régis Gasper and Erik Goormaghtigh Laboratory of Structure and Function of Biological Membranes, Center for Structural Biology and Bioinformatics, Université Libre de Bruxelles (ULB) E-mail: [email protected] This work was supported by the FNRS OBJECTIVES
3) PLS
PLS D
iscr
Discriminant model
OBJECTIVES
A discriminant PLS model was built from the 50 pixels means using the spectral range 1764 – 1300 cm-1.
Traditionally, new drugs are evaluated for their potential to kill cancer cell lines. This approach is obviously not This method determines a linear combination of variables that separates as much as possible the different sufficient, and molecules with new modes of action are required. We suggest here that the infrared spectrum of cells classes of samples. Discrimination rules are established in order to minimize within groups separation exposed to anticancer drugs could offer an opportunity to obtain a fingerprint of the metabolic changes induced by and maximize separation between groups.
these drugs. Because the infrared spectrum of cells yields a precise image of all the chemical bonds present in thesample, different drug actions are likely to each yield a unique fingerprint characteristic of the “mode of action” of the Predicted
therapeutical agent under investigation.
Topoisomerases
Antimetabolites
Antimicrotubules
AIM OF THE PROJECT : USE INFRARED SPECTROSCOPY AS A NEW SCREENING METHOD
inhibitors
SELECTING NEW ANTICANCER AGENTS ACCORDING TO THEIR MODE OF ACTION
Topoisomerases
MATERIALS AND METHODS
inhibitors
Antimetabolites
Antimicrotubules
Table 1: Percentage (%) of correctly classified mean spectra (means of 50 pixels) by the PLS model built on the1764-1300 cm-1 spectral range. About 3000 spectra not involved in the building of the model were used in this testset. Application of this PLS model to individual pixels reveals some causes of the misclassifications Antimicrotubules
Antimetabolites
Topoisomerases
inhibitors
Filtered out
Fig 1 : Cells were cultured in the absence or presence of the 7 different drugs for 48 hrs (1). Cells were detached with 0.05% trypsin/EDTA, washed 3 times with an isotonic solution (NaCl 0.9%) (2), re-suspended at ca 50,000 cells/µl and laid down Antimicrotubules
2 window (3) then an IR image (4096 Antimetabolites
pixels) was recorded between 3900 and 800 cm-1 (4). Topoisomerases
inhibitors
and are located in the correct class.
Filtered out
1) Determination of IC50
The concentration of drug reducing cell growth by 50% after 72 hrs (IC ) was determined by a MTT test for Fig 3 : Application of the PLS to a PC-3 cell culture exposed to doxorubicin (A) and mercaptopurine (B). The color of describes the result of the classification. Black pixels have been eliminated by the filters (see Methods). POTENTIAL APPLICATIONS AND KEY BENEFITS
2) Drug-induced spectral modification of the PC-3 prostate cell line
New selected
molecule
inhibitor
inhibitor
Fig 4: Hierarchical classification of the difference spectra presented in figure 3. Fig 2: Differences between mean spectra for PC-3 cells exposed to a drug as indicated in the right margin and the This method allows to rapidly classify the mode of action of potential drugs and could improve the efficiency control. A Student t-test was computed at every wavenumber with a significance level of α=0.005. Each marked CONCLUSIONS : IN THIS WORK, WE OBTAINED SPECIFIC FTIR SPECTRAL SIGNATURES FOR THE EFFECT OF 7 ANTICANCER MOLECULES ON PROSTATE TUMOR PC-3 CELLS.
FURTHERMORE, THE SIGNATURE OF DRUGS WITH SIMILAR MODES OF ACTION ARE VERY CLOSE. THIS STUDY SUGGESTS THAT FTIR IMAGING PROVIDES AN UNIQUE SIGNATURE OF
CELLULAR PATHWAYS TRIGGERED BY THE MOLECULE TESTED AND IN TURN COULD OFFER AN OBJECTIVE SELECTION CRITERION FOR NEW DRUGS WITH ORIGINAL MODES OF ACTION.

Source: http://code.ulb.ac.be/doceib2011/sites/default/files/posteraderenne_0.pdf