Reactive oxygen species and cancer paradox: To promote or to suppress?

Sehamuddin Galadari, Anees Rahman, Siraj Pallichankandy, Faisal Thayyullathil

Research output: Contribution to journalReview article

Abstract

Reactive oxygen species (ROS), a group of highly reactive ions and molecules, are increasingly being appreciated as powerful signaling molecules involved in the regulation of a variety of biological processes. Indeed, their role is continuously being delineated in a variety of pathophysiological conditions. For instance, cancer cells are shown to have increased ROS levels in comparison to their normal counterparts. This is partly due to an enhanced metabolism and mitochondrial dysfunction in cancer cells. The escalated ROS generation in cancer cells contributes to the biochemical and molecular changes necessary for the tumor initiation, promotion and progression, as well as, tumor resistance to chemotherapy. Therefore, increased ROS in cancer cells may provide a unique opportunity to eliminate cancer cells via elevating ROS to highly toxic levels intracellularly, thereby, activating various ROS-induced cell death pathways, or inhibiting cancer cell resistance to chemotherapy. Such results can be achieved by using agents that either increase ROS generation, or inhibit antioxidant defense, or even a combination of both. In fact, a large variety of anticancer drugs, and some of those currently under clinical trials, effectively kill cancer cells and overcome drug resistance via enhancing ROS generation and/or impeding the antioxidant defense mechanism. This review focuses on our current understanding of the tumor promoting (tumorigenesis, angiogenesis, invasion and metastasis, and chemoresistance) and the tumor suppressive (apoptosis, autophagy, and necroptosis) functions of ROS, and highlights the potential mechanism(s) involved. It also sheds light on a very novel and an actively growing field of ROS-dependent cell death mechanism referred to as ferroptosis.

Original languageEnglish (US)
Pages (from-to)144-164
Number of pages21
JournalFree Radical Biology and Medicine
Volume104
DOIs
StatePublished - Mar 1 2017

Keywords

  • Angiogenesis
  • Apoptosis
  • Autophagy
  • Cancer stem cells
  • Ferroptosis
  • Hydrogen peroxide
  • Metastasis
  • Necroptosis
  • ROS

ASJC Scopus subject areas

  • Biochemistry
  • Physiology (medical)

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