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Mechanisms of the synergistic effect of oral dimethyl sulfoxide on antineoplastic therapy
Abstract:
The purpose of this study was to determine whether dimethyl sulfoxide (DMSO) when administered in conjunction with antitumor drugs would potentiate their activity against a rodent tumor. Twelve compounds of diverse modes of action were examined using standard protocols of the National Cancer Institute. Median survival time and median tumor diameter were the parameters used for determining any synergistic effects of DMSO when it was ingested in the drinking water and the drug administered parenterally. The continuous ingestion of DMSO alone mixed in drinking water at concentrations between 0.25-32% was not toxic and had no effect on the tumor. Although the intraperitoneal inoculation of drugs into animals ingesting DMSO did not enhance drug effectiveness, when both DMSO and drug were added to the drinking water, it did increase antineoplastic potency. DMSO ingestion also inhibited the tumor growth rate of several parenterally administered drugs even though these same compounds failed to prolong the survival time of tumor-bearing rats. The toxicity of 12 compounds when combined with DMSO was only moderately increased in four instances. Orally ingested DMSO was found to cause a twofold increase in the concentration of labeled CPA in plasma, brain, and liver tissues. This elevation persisted for approximately two to three hours but subsequently returned to the same level as that observed in water-fed rodents. The DMSO-enhancement of tissue levels coupled with a more rapid drug rate clearance offers one explanation for the therapeutic benefit noted when oral DMSO was administered concomitantly with CPA.
Insights
Dimethyl sulfoxide (DMSO) enhances antitumor drug efficacy when administered orally with chemotherapy agents, improving antineoplastic potency and inhibiting tumor growth in rodent models. This oral DMSO administration boosts drug concentration in tissues, offering a potential therapeutic benefit.
Area of Science:
- Oncology
- Pharmacology
- Drug Discovery
Background:
- Dimethyl sulfoxide (DMSO) is a solvent with potential biological applications.
- Evaluating drug synergy is crucial for improving cancer treatment outcomes.
Purpose of the Study:
- To investigate if dimethyl sulfoxide (DMSO) potentiates antitumor drug activity against rodent tumors.
- To determine the effects of DMSO when co-administered with various chemotherapy agents.
Main Methods:
- Standard National Cancer Institute protocols were employed.
- Twelve diverse antitumor compounds were tested.
- Median survival time and tumor diameter were measured to assess synergistic effects.
- DMSO was administered via drinking water, with drugs given parenterally or orally.
Main Results:
- Oral DMSO administration, combined with drugs in drinking water, significantly increased antineoplastic potency.
- DMSO ingestion alone showed no toxicity or effect on tumor growth.
- DMSO inhibited tumor growth rate for several parenterally administered drugs.
- Oral DMSO increased CPA concentration in plasma and tissues twofold for 2-3 hours.
Conclusions:
- Oral administration of DMSO concurrently with chemotherapy drugs enhances their antineoplastic potency.
- DMSO's ability to increase drug concentration in tissues may explain observed therapeutic benefits.
- Combined oral DMSO and chemotherapy represent a promising strategy for enhancing cancer treatment efficacy.