Repozytorium publikacji - Politechnika Gdańska

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.

Autorzy

• Magdalena Niemira,
• Barbara Borowa-Mazgaj,
• Samuel B. Bader,
• Adrianna Moszyńska,
• Marcin Ratajewski link otwiera się w nowej karcie ,
• Kaja Karaś,
• Mirosław Kwaśniewski,
• Adam Krętowski,
• prof. dr hab. inż. Zofia Mazerska link otwiera się w nowej karcie ,
• Prof. Ester M. Hammond,
• dr inż. Anna Skwarska