Apoptotic signaling through reactive oxygen species in cancer cells

Abstract

Reactive oxygen species (ROS) take part in diverse biological processes like cell growth, programmed cell death, cell senescence, and maintenance of the transformed state through regulation of signal transduction. Cancer cells adapt to new higher ROS circumstance. Sometimes, ROS induce cancer cell proliferation. Meanwhile, elevated ROS render cancer cells vulnerable to oxidative stress-induced cell death. However, this prominent character of cancer cells allows acquiring a resistance to oxidative stress conditions relative to normal cells. Activated signaling pathways that increase the level of intracellular ROS in cancer cells not only render up-regulation of several genes involved in cellular proliferation and evasion of apoptosis but also cause cancer cells and cancer stem cells to develop a high metabolic rate. In over the past several decades, many studies have indicated that ROS play a critical role as the secondary messenger of tumorigenesis and metastasis in cancer from both in vitro and in vivo. Here we summarize the role of ROS and anti-oxidants in contributing to or preventing cancer. In addition, we review the activated signaling pathways that make cancer cells susceptible to death.

Keywords: Oxidative stress, Reactive oxygen species, Carcinogenesis, Apoptosis, Signal transduction, Antioxidants

Core tip: Reactive oxygen species originally used to induce injurious cellular effects are now recognized as key physiological molecules for the induction of host defense genes, activation of transcription factors, and regulation of signal transduction. Tumorigenic cells can induce a new redox balance, resulting in cellular adaptation and proliferation. Here, we review the role of oxidative stress in cancer cells using a pathophysiological view.