RT Journal Article
T1 Radiosensitisation of human colorectal cancer cells by ruthenium(II) arene anticancer complexes
A1 Carter, R.
A1 Westhorpe, A.
A1 Romero Castro, María José
A1 Habtemariam, A.
A1 Gallevo, C. R.
A1 Bark, Y.
A1 Menezes, N.
A1 Sadler, P. J.
A1 Sharma, R. A.
K1 Drug discovery
K1 Rectal cancer
K1 Ruthenium
AB Some 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 cancer
PB Springer Nature
YR 2016
FD 2016-02-12
LK https://hdl.handle.net/10347/44310
UL https://hdl.handle.net/10347/44310
LA eng
NO Carter, 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, 20596/1-20596/12
NO This document is the published version of the work which is available as an open access article at https://doi.org/10.1038/srep20596
NO We acknowledge funding from the ERC (grant no. 247450), EPSRC (grant no. EP/F034210/1), Birmingham Science City/EU ERDF/AWM, Fundación Barrié (Spain), NIHR Biomedical Research Centre Oxford, CRUK Oxford Centre, Experimental Cancer Medicines Centre. We thank Mick Woodcock for assistance with FACS analysis, and colleagues in the EC COST Action CM1105 for stimulating discussions.
DS Minerva
RD 21 may 2026