Say No to DMSO: Dimethylsulfoxide Inactivates Cisplatin, Carboplatin, and Other Platinum Complexes

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 dimethylsulfoxide (DMSO). However, dissolving cisplatin in DMSO for laboratory-based studies results in ligand displacement and changes 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.

Expression of Organic Anion Transporter 1 or 3 in Human Kidney Proximal Tubule Cells Reduces Cisplatin Sensitivity

“…These did not affect the cytotoxicity after 24 hours nor after 7 days of pre-exposure, suggesting that OAT-mediated influx is not directly involved in reducing cisplatin sensitivity, nor that OAT transport results in the induction of protective cellular changes in the long term (Table 1). It should be noted that 7-day exposure to competitive inhibitor solvent (DMSO, 0.1% v/v) slightly reduced cisplatin-induced toxicity, which may be explained by inactivation of the drug by prolonged exposure to DMSO (Table 1) (Hall et al, 2014). To avoid possible adaptive responses that may have affected drug sensitivity, cisplatin preconditioning at shorter incubation times was not performed.…”

Organometallic cobalamin anticancer derivatives for targeted prodrug delivery via transcobalamin-mediated uptake

“…In interpreting the value of 1, it must be considered that dissolving platinum complexes in DMSO often results in ligand displacement and changes to the structure of the complex. 27,28 However, due to its very low aqueous solubility, a dissolution in DMSO (0.1% final concentration) was necessary. The activity of 3 is remarkable since its IC 50 of 1.4 μM is lower than cisplatin.…”

Cisplatin-induced apoptosis in non-small-cell lung cancer cells is dependent on Bax- and Bak-induction pathway and synergistically activated by BH3-mimetic ABT-263 in p53 wild-type and mutant cells

“…The primer and probe sets used were predesigned primer/probe sets: β-actin, were treated with 20 µM cisplatin (IC 50 was determined as 12 µM and 8 µM, respectively) solved in water to prevent solvent-mediated inactivation [24]. As shown in …”