Abstract
Although numerous studies have demonstrated the biological and multifaceted nature of dimethyl sulfoxide (DMSO) across different in vitro models, the direct effect of “non-toxic” low DMSO doses on cardiac and cancer cells has not been clearly explored. In the present study, H9c2 cardiomyoblasts and MCF-7 breast cancer cells were treated with varying concentrations of DMSO (0.001–3.7%) for 6 days. Here, DMSO doses < 0.5% enhanced the cardiomyoblasts respiratory control ratio and cellular viability relative to the control cells. However, 3.7% DMSO exposure enhanced the rate of apoptosis, which was driven by mitochondrial dysfunction and oxidative stress in the cardiomyoblasts. Additionally, in the cancer cells, DMSO (≥0.009) led to a reduction in the cell’s maximal respiratory capacity and ATP-linked respiration and turnover. As a result, the reduced bioenergetics accelerated ROS production whilst increasing early and late apoptosis in these cells. Surprisingly, 0.001% DMSO exposure led to a significant increase in the cancer cells proliferative activity. The latter, therefore, suggests that the use of DMSO, as a solvent or therapeutic compound, should be applied with caution in the cancer cells. Paradoxically, in the cardiomyoblasts, the application of DMSO (≤0.5%) demonstrated no cytotoxic or overt therapeutic benefits.
Highlights
Dimethyl sulfoxide (DMSO) is a versatile compound that is extensively used as a solvent in pharmacology and toxicology to enhance drug delivery, and dissolve numerous drugs and herbal extracts
We demonstrated that cardiomyoblasts have an inherently lower energy phenotype than breast cancer cells, which presented with a significantly higher oxygen consumption rate (OCR) and glycolytic profile
The findings of this study further demonstrated that the rate of apoptosis in the cardiomyoblasts treated with the “non-toxic” low dimethyl sulfoxide (DMSO) doses (≤0.5%) was comparable to the severity of apoptosis observed in the untreated control group
Summary
Dimethyl sulfoxide (DMSO) is a versatile compound that is extensively used as a solvent in pharmacology and toxicology to enhance drug delivery, and dissolve numerous drugs and herbal extracts. In recent years, increasing evidence has demonstrated that the amphiphilic nature of DMSO allows it to influence diverse biological and medical processes, such as disease pathology and intervention [1,2]. The applied concentrations of DMSO are often unreported due to its obvious and frequent use [3]. The influence that DMSO has on cellular mechanisms has been implicated in the modifications of essential cellular structures, such as proteins and DNA, and has been studied for its involvement in cancer and cardiovascular diseases [6,7]
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