Effective targeting of RNA polymerase I in treatment-resistant prostate cancer.

ABSTRACT:

Background

Advanced prostate cancers depend on protein synthesis for continued survival and accelerated rates of metabolism for growth. RNA polymerase I (Pol I) is the enzyme responsible for ribosomal RNA (rRNA) transcription and a rate-limiting step for ribosome biogenesis. We have shown using a specific and sensitive RNA probe for the 45S rRNA precursor that rRNA synthesis is increased in prostate adenocarcinoma compared to nonmalignant epithelium. We have introduced a first-in-class Pol I inhibitor, BMH-21, that targets cancer cells of multiple origins, and holds potential for clinical translation.

Methods

The effect of BMH-21 was tested in prostate cancer cell lines and in prostate cancer xenograft and mouse genetic models.

Results

We show that BMH-21 inhibits Pol

SUBMITTER: Low JY 

PROVIDER: S-EPMC7025478 | biostudies-literature | 2019 Dec

REPOSITORIES: biostudies-literature