Say no to DMSO: dimethylsulfoxide inactivates cisplatin, carboplatin, and other platinum complexes
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Abstract
The platinum drugs cisplatin, carboplatin, and oxaliplatin are highly utilized in the clinic and as a consequence are extensively studied in the laboratory setting. In this study, we examined the literature and found a significant number of studies (11%–34%) in prominent cancer journals utilizing cisplatin dissolved in DMSO. However, dissolving cisplatin in DMSO for laboratory-based studies results in ligand displacement and changes to the structure of the complex. We examined the effect of DMSO on platinum complexes, including cisplatin, carboplatin, and oxaliplatin, finding that DMSO reacted with the complexes, inhibited their cytotoxicity and their ability to initiate cell death. These results render a substantial portion of the literature on cisplatin uninterpretable. Raising awareness of this significant issue in the cancer biology community is critical, and we make recommendations on appropriate solvation of platinum drugs for research. Cancer Res; 74(14); 3913–22. ©2014 AACR.
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Cisplatin has formulation issues including relatively low solubility in both aqueous and organic solvents.
“Moreover, cisplatin also has formulation issues such as relatively low solubility in both aqueous and organic solvents [6].”
From Co-delivery of Paclitaxel and Cisplatin in Poly(2-oxazoline) Polymeric Micelles: Implications for Drug Loading, Release, Pharmacokinetics and Outcome of Ovarian and Breast Cancer Treatments (2019) · cites this paper as [6]
The Introduction describes relatively low solubility as a limitation for platinum drugs, and the Results give cisplatin’s maximum aqueous solubility as just over 3 mM. The Results also report that several organic solvents dissolved 10 mM cisplatin, although acetonitrile and Cremophor EL did not fully dissolve it. The paper therefore supports an aqueous formulation limitation but not the broader claim of relatively low solubility in organic solvents generally. (LLM, conf=0.84)
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References 57 · Cited by 377
Research works printed but not linked: 1
- [44]Shen DW Pouliot LM Hall MD Gottesman MM Cisplatin resistance: a cellular self-defense mechanism resulting from multiple epigenetic and genetic changes Pharmacol Rev 2012 64 706 21 22659329 PMC3400836
- Authors
- Hall, M. D., Telma, K. A., Chang, K.-E., Lee, T. D., Madigan, J. P., Lloyd, J. R., Goldlust, I. S., Hoeschele, J. D., & Gottesman, M. M.
- Affiliations
- National Cancer Institute (UA)
- National Institutes of Health (US)
- Eastern Michigan University (US)
- Corresponding author
- Gottesman, Michael M.
- ORCID
- Venue
- Cancer Research
- Published
- 2014-07-14
- Volume
- 74
- Issue
- 14
- Pages
- 3913-3922
- ISSN
- 0008-5472 (ISSN-L)
- 1538-7445
- PMC
- PMC4153432
- OpenAlex
- W1965889589
- Cited by
- 377
- References
- 57
- Citations by year
- 2026: 12 · 2025: 32 · 2024: 30 · 2023: 38 · 2022: 38 · 2021: 37 · 2020: 42 · 2019: 32 · 2018: 37 · 2017: 33 · 2016: 25 · 2015: 15 · 2014: 6
- FWCI
- 12.70
- Type
- journal article
- Language
- en
- Open access
- green
- www.ncbi.nlm.nih.gov
- Locations
- Cancer Research (publishedVersion)
- PubMed (publishedVersion)
- Europe PMC (PubMed Central) (acceptedVersion)
- PubMed Central (acceptedVersion)
- Funders
- Howard Hughes Medical Institute
- National Institutes of Health (Z99 TR999999)
- National Cancer Institute (ZIABC010830)
- Topics
- Health Sciences › Medicine › Oncology › Metal complexes synthesis and properties
- Life Sciences › Biochemistry, Genetics and Molecular Biology › Molecular Biology › Cancer therapeutics and mechanisms
- Physical Sciences › Chemistry › Organic Chemistry › Inorganic and Organometallic Chemistry
- Keywords
- dimethyl sulfoxide, cisplatin, carboplatin, oxaliplatin, platinum anticancer drugs, ligand displacement, drug inactivation, cytotoxicity, cell death, research reproducibility, DMSO toxicity
- MeSH terms
- Antineoplastic Agents, Cisplatin, Dimethyl Sulfoxide, Humans, Solvents, Carboplatin, Platinum Compounds, Inhibitory Concentration 50, Cell Line, Tumor
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