Is Olomoucine, a Weak CDK2 Inhibitor, Able to Induce Apoptosis in Cancer Cells?

Content Provider	Scilit
Author	Wandl, Stefanie Węsierska-Gądek, Józefa
Copyright Year	2009
Description	Journal: Annals of the New York Academy of Sciences Olomoucine (OLO), a substituted purine analogue, is a much weaker inhibitor of cyclin-dependent kinases than other closely related ATP derivatives. It has been recently reported that OLO did not affect the viability of normal human MRC-5 fibroblasts, but it inhibited the proliferation of human HL-60 leukemia cells. Therefore, it was interesting to explore the antiproliferative effect of OLO and to characterize its action on distinct human cancer cells differing in the functional status of the cell cycle. Human HeLa cervical carcinoma and HL-60 leukemia cells were continuously exposed to increasing concentrations of OLO for 24 h and 48 h or alternatively, cells after treatment for 24 h were postincubated in a drug-free medium. Surprisingly, OLO more strongly affected the proliferation of HL-60 cells than that of HeLa cells. Flow cytometric analyses revealed that OLO at higher doses increases the frequency of a hypoploid HL-60 cell population representing cells undergoing apoptosis. These results substantiated the data of the determination of the number of viable cells. Moreover, OLO at higher doses modulates the cell cycle progression of tested cancer cells. Detailed analyses of the DNA concentration in single cells revealed that OLO-mediated reduction of the number of G(1)-phase cells was accompanied by an increase of the frequency of G(2)-phase cells. The kinetics of these changes differed between both tested cancer cell lines, suggesting that some cancer cells exhibit increased susceptibility to OLO action. It remains to clarify whether the strong proapoptotic effect of OLO observed in HL-60 cells depends on their differentiation status.
Related Links	http://onlinelibrary.wiley.com/doi/10.1111/j.1749-6632.2009.04700.x/pdf
Ending Page	249
Page Count	8
Starting Page	242
e-ISSN	17496632
DOI	10.1111/j.1749-6632.2009.04700.x
Journal	Annals of the New York Academy of Sciences
Issue Number	1
Volume Number	1171
Language	English
Publisher	Wiley-Blackwell
Publisher Date	2009-08-15
Access Restriction	Open
Subject Keyword	Journal: Annals of the New York Academy of Sciences Pharmacological Cdk Inhibitors G1 Arrest Cell Cycle Arrest P53 Tumor Suppressor
Content Type	Text
Resource Type	Article