Transcriptional profiling reveals a potent activity of
anticancer imidazoacridinone C-1311 against prostate
cancer cells expressing androgen receptor
M. Niemira1
, A. Bielska1
, Z. Mazerska2
, M. Kwasniewski3
,
A. Kretowski1
, A. Skwarska2
1
Centre Clinical Research, Medical University of Bialystok,
Bialystok, Poland, 2
Department of Pharmaceutical Technology
and Biochemistry, Chemical Faculty, Gdansk University of
Technology, Gdansk, Poland, 3
Centre for Bioinformatics and
Data Analysis, Medical University of Bialystok, Bialystok,
Poland
Introduction: The androgen receptor (AR) plays critical
role in the poor response of androgen-dependent and
castrate-resistant prostate cancers to chemotherapy. Anticancer imidazoarcidinone C-1311 (Symadex™) is a new
inhibitor of topisomerase II and receptor tyrosine kinase
FLT3 that has been tested in phase II studies against
metastatic breast cancer. Here, we assessed the effect of C1311 on the transcriptional profiles in prostate cancer cell
lines with different AR status.
Materials and Methods: Prostate cancer cells were
exposed to C-1311 for 24 h. Global transcriptome profiling
for LNCaP (AR+) and DU-145 (AR-) cells was performed
Abstracts from the 51st European Society of Human Genetics Conference: Posters 395
using Illumina Hiseq 4000 platform. The biological
relevance of dysregulated transcripts was assessed by
Ingenuity Pathway Analysis (IPA) software.
Results: IPA analysis of transcripts uniquely expressed in
LNCaP and DU-145 cells exposed to C-1311 revealed
activation of diverse signalling pathways depending on AR
status. The main enriched top canonical pathways identified
in LNCaP (AR+) cells were associated with multiple cell
cycle control and survival processing genes like ATM and
breast cancer signalling whereas glycolysis, gluconeogenesis and lipid metabolism pathways were predominantly
dysregulated in DU-145 (AR-) cells. Furthermore, the main
upstream regulators and their target genes in both cell lines
were involved in the different biological processes.
Conclusion: Taken together, our finding suggest that AR
status may significantly affect the efficacy of C-1311
against prostate cancer cells. Association of specific
canonical pathways indicates the opposite mechanism of
action of imidazoacridinone C-1311 in both androgendependent and independent prostate cancer. Founded by the
National Science Centre, Grant No 2013/09/D/NZ7/04185.
M. Niemira: None. A. Bielska: None. Z. Mazerska:
None. M. Kwasniewski: None. A. Kretowski: None. A.
Skwarska: None.
