Neoplasma Vol.51, p.358-367, 2004
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| Title: Synergic effects of the cyclin-dependent kinase (CDK) inhibitor
olomoucine and androgen-antagonist bicalutamide on prostatic
cancer cell lines
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| Author: Z., KOLAR
; J., KNILLOVA
; J., BOUCHAL
; A., HLOBILKOVA
; M., STRNAD
; |
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Abstract: Currently, mechanisms leading to both apoptosis induction and the
development of hormone-independence of prostate carcinoma cells
are intensively studied. Attention is also given to the
possibility of restoring cell sensitivity to hormone-antagonists.
The present study focuses on the effect of the combined synthetic
cyclin-dependent kinase [CDK] inhibitor, olomoucine and the
antiandrogen bicalutamide on hormone-insensitive (DU-145) and
hormone-sensitive (LNCaP) prostate cancer cell lines. In both cell
lines reduction in cell viability was significantly higher when
olomoucine and bicalutamide were applied in combination when
compared to separate application of both these drugs. The setting
of optimal concentrations for both substances was important for
the final effect on both cell lines. The proliferation arrest was
accompanied by a decrease in cyclin D1 expression and the
activation of p21Waf1/Cip1 and p27Kip1 pathways in both cell
lines. Contrary to the previously described effect of 200 uM
olomoucine, weak AR induction after treatment with effective
concentrations of olomoucine was not seen in the hormone-
insensitive cell line DU-145. The related reaction of DU-145 and
LNCaP cell lines to treatment with combined olomoucine and
bicalutamide likely provides evidence that the inhibitory effect
of bicalutamide may not only be associated with its antiandrogenic
properties. The tested substances probably influence different
regulatory pathways and these have co-operative impact on the cell
cycle outcome. Understanding antitumor and antihormone actions of
both agents is essential for the development of novel therapeutic
schemes integrating substances with different action. Our results
show that the combination of synthetic CDK inhibitors and hormone-
antagonists may be one of a number of possible alternatives.
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| Keywords: prostate cancer, bicalutamide, olomoucine, cyclin-dependent
kinase, proliferation, apoptosis
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| Year: 2004, Volume: 51, Issue: |
Page From: 358, Page To: 367 |
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