Comprehension of the Relationship between Autophagy and Reactive Oxygen Species for Superior Cancer Therapy with Histone Deacetylase Inhibitors

Abstract

Epigenetics contains various mechanisms by which cells employ to regulate the transcription of many DNAs. Histone acetylation is an obvious example of the epigenetic mechanism regulating the expression of several genes by changing chromatin accessibility. Histone deacetylases (HDACs) are a class of enzymes that play a critical role in the epigenetic regulation by deacetylation of histone proteins. Inhibitors of the histone deacetylase could result in hyperacetylation of histones, which eventually induce various cellular consequences such as generation of reactive oxygen species (ROS), activation of apoptotic pathways, and initiating autophagy. In particular, excessive levels of ROS have been proposed to contribute to the pathophysiology of various diseases including cancer. Cancers are, as it were, a class of redox diseases. Low levels of ROS are beneficial for cells, however, cancer cells generally have high levels of ROS, which makes them more susceptible than normal cells to the further increases of ROS levels. Cancer cells exhibit metabolic alterations for managing to sustain these oxidative stresses. There is a growing interest in the use of HDAC inhibitors as promising cancer therapeutics with potentiating the activity of established therapeutic applications. Therefore, it should be important to understand the underlying relationship between the regulation of HDACs, ROS production, and cancer cell biology.

Fatty Acid Metabolites and the Tumor Microenvironment as Potent Regulators of Cancer Stem Cell Signaling

“…However, resistance to chemotherapy and radiation is frequently observed, likely because of the intrinsic properties of cancer stem cells acquired through multiple interactions with the tumor microenvironment, including dysregulation of the drug–efflux pump system and DNA repair capacity [ 52 , 53 , 54 ]. The failure of cancer therapy is a current major concern, with resistance to conventional cancer therapies considered the most serious [ 55 , 56 ]. Resistance can be acquired by various mechanisms.…”

Bazı etanolik bitki ekstrelerinin histon deasetilaz inhibitör ve antioksidan aktiviteleri: Kanser için yeni bir terapötik yaklaşım

“…evidence suggests that dietary phytochemicals possessing HDAC inhibitory activity can be used to repair mechanisms in cancer cells 21 . An imbalance between acetylation and deacetylation changes the structure and the activity of histone proteins, influencing tumor cell functions such as gene expression, cell growth and/or survival, and cell death pathways 22 .…”

Promising Tactics with Certain Probiotics for the Treatment of Nephropathy in Hematopoietic Stem Cell Transplantation

“…The gut microbiota can protect and/or damage host cells/organs, including kidney cells, contributing to the homeostasis of the health-disease balance in the host [35]. Generally, ROS are released by cells as a result of ATP synthesis and can damage cellular DNA [36,37]. Some physiological roles of ROS include the regulation of enzymes involved in autophagy, DNA synthesis, and DNA repair [38].…”

“…The ROS comprise oxygen-containing energetic molecules capable of reacting with various organic molecules produced due to inflammatory reactions [39]. Certain levels of ROS can alter the signaling pathways to control mRNA and/or protein expression, and in turn, influence cell survival [36,40]. Gut microbiota might also influence cell survival in some cases.…”