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Anticancer Imidazoacridinone C-1311 is Effective in Androgen-Dependent and Androgen-Independent Prostate Cancer Cells
Abstract
Androgen receptor (AR) plays a crutial role in prostate cancer (PCa) development and metastasis. Here, we reported potent anti-PCa activity of a small molecule imidazoacridinone C-1311. In AR-positive PCa cells, C-1311 was found to inhibit the transcriptional activity of AR uncovering a novel mechanism that may be relevant for its anticancer effect. Mechanistically, C-1311 decreased AR binding to prostate-specific antigen (PSA) promoter, reduced PSA protein level, and as shown by transcriptome sequenvcing, down-regulated numerous AR target genes. Importantly, AR-negative PCa cells were also sensitive to C-1311, suggesting a promising efficacy in androgen-independent PCa sub-type. Irrespective of AR status, C-1311 induced DNA damage, arrested cell cycle progression and induced apoptosis. RNA sequencing indicated on the significant differences in transcriptional response to C-1311 between PCa cells. Gene ontology analysis showed that in AR-dependent PCa cells, C-1311 mainly affected DNA damage response pathways. In contrast, in AR-independent PCa cells, C-1311 targeted cellular metabolism and inhibited gene regulating glycolysis and gluconeogenesis. Together, these results indicate that C-1311 warrants further development for the treatment of PCa.
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Authors (11)
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Magdalena Niemira
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Barbara Borowa-Mazgaj
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Samuel B. Bader
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Adrianna Moszyńska
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Kaja Karaś
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Mirosław Kwaśniewski
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Adam Krętowski
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Ester M. Hammond Prof.
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Anna Skwarska dr inż.
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- Category:
- Articles
- Type:
- artykuły w czasopismach
- Published in:
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Biomedicines
no. 8,
ISSN: 2227-9059 - Language:
- English
- Publication year:
- 2020
- Bibliographic description:
- Niemira M., Borowa-Mazgaj B., Bader S., Moszyńska A., Ratajewski M., Karaś K., Kwaśniewski M., Krętowski A., Mazerska Z., Hammond E., Skwarska A.: Anticancer Imidazoacridinone C-1311 is Effective in Androgen-Dependent and Androgen-Independent Prostate Cancer Cells// Biomedicines -Vol. 8,iss. 9 (2020), s.292-
- DOI:
- Digital Object Identifier (open in new tab) 10.3390/biomedicines8090292
- Verified by:
- Gdańsk University of Technology
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