The major contribution of the DNA damage-triggered reactive oxygen species production to cell death: implications for antimicrobial and cancer therapy

Abstract

Genotoxic agents damage DNA, block DNA replication and provoke cell death. However, there is growing evidence that an important part of their cytotoxicity results from metabolic disturbances induced by treatment. This review article describes how increased production of the reactive oxygen species (ROS) induced by different genotoxic agents contribute to death of prokaryotic and eukaryotic cells. ROS are byproducts of normal cellular functioning. Because ROS are damaging cellular macromolecules, they are constantly eliminated by protective antioxidant mechanisms. However, even a small increase in ROS production may have deleterious consequences because cells possess just enough defensive mechanisms to protect themselves against endogenously produced ROS. Therefore, it may be possible to enhance cytotoxic potential of antimicrobial and anticancer drugs by increasing ROS production or by inhibiting cellular antioxidant systems.

Incomplete base excision repair contributes to cell death from antibiotics and other stresses

“…This phenomenon of bacterial cell death caused by incomplete BER has been extensively documented [6,7,[10], [11], [12], [13], [14], [15], [16], [17]], but its relevance to antibiotic lethality has only recently been appreciated. In this review, we will summarize the evidence for this pathway of cell death in bacteria and draw parallels to similar results in eukaryotes.…”

Per- and polyfluoroalkyl substances impact human spermatogenesis in a stem-cell-derived model

“…Certain environmental toxicants have been shown to induce oxidative stress (Maiorino and Ursini 2002; Aly 2013; Erkekoglu and Kocer-Gumusel 2014) even in our in vitro model (Easley et al 2015). However, ROS production does not always induce cell death (Matic 2017). Reactive oxygen species are extremely volatile genotoxic agents capable of damaging DNA and oxidizing proteins (Matic 2017).…”

“…However, ROS production does not always induce cell death (Matic 2017). Reactive oxygen species are extremely volatile genotoxic agents capable of damaging DNA and oxidizing proteins (Matic 2017). An increase in ROS could lead to DNA mutations capable of being transmitted to future generations.…”

A Significant Question in Cancer Risk and Therapy: Are Antibiotics Positive or Negative Effectors? Current Answers and Possible Alternatives

“…Alternatively, efforts should be made to identify or develop new antibiotics that may have both antimicrobial and anti-tumor activities [163,164]. The selection of antibiotics with anti-tumor activity may be done by taking into consideration: (a) their mechanism of action, by taking advantage of properties such as their genotoxicity [165,166], their apoptosis-inducing potential [167,168], their ability to block tumor-specific signaling pathways [169], their epigenetic modulatory effects [170,171], or other relevant molecular mechanisms [172,173]; and (b) the lowest possible deleterious effects on the microbiota, as in the case of rifaximin [174,175], that has broad-spectrum against both Gram-positive and Gram-negative bacteria and, on the basis of its unique absorbability, solubility and pharmacokinetic properties may in fact correct microbiota dysbiotic imbalances [176].…”