4.6 Article

The Implication of Low Dose Dimethyl Sulfoxide on Mitochondrial Function and Oxidative Damage in Cultured Cardiac and Cancer Cells

Journal

MOLECULES
Volume 26, Issue 23, Pages -

Publisher

MDPI
DOI: 10.3390/molecules26237305

Keywords

mitochondria; bioenergetics; oxidative stress; apoptosis

Funding

  1. South African Medical Research Council (SAMRC), through its division of the Biomedical Research and Innovation Platform (baseline funding)
  2. National Research Foundation (NRF) Thuthuka Programme [UID120812]
  3. SAMRC through its Division of Research Capacity Development

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The study found that DMSO concentrations lower than 0.5% can enhance respiratory control ratio and cellular viability in cardiomyoblasts, while exposure to 3.7% DMSO increases apoptosis in cardiomyoblasts due to mitochondrial dysfunction and oxidative stress. In cancer cells, DMSO at concentrations equal to or higher than 0.009 reduces maximal respiratory capacity and ATP-linked respiration, leading to increased ROS production and apoptosis. Surprisingly, 0.001% DMSO exposure resulted in increased proliferative activity in cancer cells. These findings suggest caution when using DMSO in cancer cells, while demonstrating no cytotoxic effects or therapeutic benefits at concentrations equal to or lower than 0.5% in cardiomyoblasts.
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.

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