Carter, R.Westhorpe, A.Romero Castro, María JoséHabtemariam, A.Gallevo, C. R.Bark, Y.Menezes, N.Sadler, P. J.Sharma, R. A.2025-12-092025-12-092016-02-12Carter, R., Westhorpe, A., Romero, M. J., Habtemariam, A., Gallevo, C. R., Bark, Y., Menezes, N., Sadler, P J., Sharma, R. A. (2016). "Radiosensitisation of human colorectal cancer cells by ruthenium(II) arene anticancer complexes", Sci. Rep., 6, 20596/1-20596/12https://hdl.handle.net/10347/44310This document is the published version of the work which is available as an open access article at https://doi.org/10.1038/srep20596Some of the largest improvements in clinical outcomes for patients with solid cancers observed over the past 3 decades have been from concurrent treatment with chemotherapy and radiotherapy (RT). The lethal effects of RT on cancer cells arise primarily from damage to DNA. Ruthenium (Ru) is a transition metal of the platinum group, with potentially less toxicity than platinum drugs. We postulated that ruthenium-arene complexes are radiosensitisers when used in combination with RT. We screened 14 ruthenium-arene complexes and identified AH54 and AH63 as supra-additive radiosensitisers by clonogenic survival assays and isobologram analyses. Both complexes displayed facial chirality. At clinically relevant doses of RT, radiosensitisation of cancer cells by AH54 and AH63 was p53-dependent. Radiation enhancement ratios for 5–10 micromolar drug concentrations ranged from 1.19 to 1.82. In p53-wildtype cells, both drugs induced significant G2 cell cycle arrest and apoptosis. Colorectal cancer cells deficient in DNA damage repair proteins, EME1 and MUS81, were significantly more sensitive to both agents. Both drugs were active in cancer cell lines displaying acquired resistance to oxaliplatin or cisplatin. Our findings broaden the potential scope for these drugs for use in cancer therapy, including combination with radiotherapy to treat colorectal cancereng© 2016, The Author(s). Open access article (https://www.nature.com/articles/srep20596#citeas). This work is licensed under a Creative Commons Attribution 4.0 International License (CC BY 4.0; http://creativecommons.org/licenses/by/4.0/). The images or other third party material in this article are included in the article’s Creative Commons license, unless indicated otherwise in the credit line; if the material is not included under the Creative Commons license, users will need to obtain permission from the license holder to reproduce the material.Attribution 4.0 Internationalhttp://creativecommons.org/licenses/by/4.0/Drug discoveryRectal cancerRutheniumjournal article10.1038/srep205962045-2322open access