Cancers, Vol. 11, Pages 1429: The Targeting of RNA Polymerase I Transcription Using CX-5461 in Combination with Radiation Enhances Tumour Cell Killing Effects in Human Solid Cancers

Cancers, Vol. 11, Pages 1429: The Targeting of RNA Polymerase I Transcription Using CX-5461 in Combination with Radiation Enhances Tumour Cell Killing Effects in Human Solid Cancers Cancers doi: 10.3390/cancers11101429 Authors: Mohammed Ismael Roger Webb Mazhar Ajaz Karen J. Kirkby Helen M. Coley An increased rate of cellular proliferation is a hallmark of cancer and may be accompanied by an increase in ribosome biogenesis and dysregulation in rRNA synthesis. In this regard, CX-5461 has been developed as a novel RNA polymerase I inhibitor and is currently in Phase I/II clinical trials for solid and hematological malignancies. In the present study, interactions between CX-5461 and single-dose X-ray exposure were assessed using isobologram analysis using MTS assay and drug-induced cell death was assessed using flow cytometric, confocal microscopy and Western blot analysis. Combination treatments involving CX-5461 and single-dose X-ray exposure highlighted increased effectiveness compared to individual treatment alone in the CaSki cervical cancer line, with marked synergistic interaction occurring within the low-drug (50 nM) and low-dose radiation range (2–6 Gy). Cell lines challenged with CX-5461 demonstrated the presence of DNA damage, induction of apoptosis, autophagy and senescence alongside high percentages of G2/M cell cycle arrest. In addition, we report preferential sensitivity of ovarian cancer cells with BRCA2 mutation to this novel agent....
Source: Cancers - Category: Cancer & Oncology Authors: Tags: Article Source Type: research