A MULTIPARAMETER APPROACH TO CELL CYCLE ANALYSIS AS A STANDARD TOOL IN ONCOLOGY DRUG DISCOVERY - Flow Cytometry in Drug Discovery and Development - page 114

FIGURE 5.13 Apoptotic (green) activity evaluationmapped to proliferating (blue) cells after
cisplatin treatments and to quiescent (red) cells after BMS-214662 treatment. (See the color
version of the figure in the Color Plates section.)
several different activities on cells. This was done by linking cell cycle profiles
(obtained from DNA staining) to proliferating activity measured by incorporation of
BrdU and to PARP cleavage. All these activities were measured simultaneously in the
same cell along different time points and culture conditions. This experimental design
enabled us to demonstrate that those cells dying by the effect of BMS-214662 were at
the G 1 phase of the cell cycle (see Figure 5.13) [47]. Furthermore, this observation
pointed at the possibility that this drug may target quiescent cells, such as those
described as cancer stem cells.
5.5 CONCLUSIONS
The use of a multiparameter approach tailored to be a selective screen, as described in
this chapter, provides a broader understanding of the various mechanisms of action
exhibited by specific compounds and permits the visualization of multiple effects at a
glance in a drug screening approach that can improve the selection of compounds with
a greater opportunity for entry into pharmaceutical development.
As this publication goes into print, the status of the compounds used as examples in
this chapter is as follows:
BMS-250749 is on hold from further developments due to other priorities.
BMS-214662 is being reevaluated for activities toward cancer stem cells [48].
BMS-247550 is successfully being used in the clinic and is marketed under the
name of IXEMPRA.