Back to Search
Start Over
Radiosensitisation of human colorectal cancer cells by ruthenium(II) arene anticancer complexes
- Source :
- Scientific Reports
- Publication Year :
- 2016
- Publisher :
- Springer Science and Business Media LLC, 2016.
-
Abstract
- 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.
- Subjects :
- 0301 basic medicine
Drug
DNA Repair
Organoplatinum Compounds
Colorectal cancer
medicine.medical_treatment
media_common.quotation_subject
Antineoplastic Agents
Apoptosis
Bioinformatics
Radiation Tolerance
Ruthenium
Article
03 medical and health sciences
0302 clinical medicine
Cell Line, Tumor
Organometallic Compounds
Humans
Medicine
media_common
Cisplatin
Chemotherapy
Multidisciplinary
business.industry
Cell Cycle Checkpoints
medicine.disease
3. Good health
Oxaliplatin
Solutions
Radiation therapy
030104 developmental biology
Drug Resistance, Neoplasm
030220 oncology & carcinogenesis
Cancer cell
Cancer research
Tumor Suppressor Protein p53
Colorectal Neoplasms
business
DNA Damage
medicine.drug
Subjects
Details
- ISSN :
- 20452322
- Volume :
- 6
- Database :
- OpenAIRE
- Journal :
- Scientific Reports
- Accession number :
- edsair.doi.dedup.....3bd6c0ee94a296e5d34367ddcd8342a5