title: Overproduction of reactive oxygen species - obligatory or not for induction of apoptosis by anticancer drugs.
abstract: Many studies demonstrate that conventional anticancer drugs elevate intracellular level of reactive oxygen species (ROS) and alter redox-homeostasis of cancer cells. It is widely accepted that anticancer effect of these chemotherapeutics is due to induction of oxidative stress and ROS-mediated apoptosis in cancer. On the other hand, the harmful side effects of conventional anticancer chemotherapy are also due to increased production of ROS and disruption of redox-homeostasis of normal cells and tissues. This article describes the mechanisms for triggering and modulation of apoptosis through ROS-dependent and ROS-independent pathways. We try to answer the question: "Is it possible to induce highly specific apoptosis only in cancer cells, without overproduction of ROS, as well as without harmful effects on normal cells and tissues?" The review also suggests a new therapeutic strategy for selective killing of cancer cells, without significant impact on viability of normal cells and tissues, by combining anticancer drugs with redox-modulators, affecting specific signaling pathways and avoiding oxidative stress.
authors.affiliation: Medical Faculty, Trakia University, Stara Zagora 6000, Bulgaria.
authors.forename: Donika
authors.initials: D
authors.lastname: Ivanova
authors.affiliation: Medical Faculty, Trakia University, Stara Zagora 6000, Bulgaria; Institute of Biophysics & Biomedical Engineering, Bulgarian Academy of Sciences, Sofia 1113, Bulgaria.
authors.forename: Zhivko
authors.initials: Z
authors.lastname: Zhelev
authors.affiliation: Department of Molecular Imaging and Theranostics, National Institute of Radiological Sciences, National Institute for Quantum and Radiological Science and Technology, Chiba 263-8555, Japan.
authors.forename: Ichio
authors.initials: I
authors.lastname: Aoki
authors.affiliation: Department of Molecular Imaging and Theranostics, National Institute of Radiological Sciences, National Institute for Quantum and Radiological Science and Technology, Chiba 263-8555, Japan; Medical Faculty, Sofia University, Sofia 1407, Bulgaria.
authors.forename: Rumiana
authors.initials: R
authors.lastname: Bakalova
authors.affiliation: Department of Molecular Imaging and Theranostics, National Institute of Radiological Sciences, National Institute for Quantum and Radiological Science and Technology, Chiba 263-8555, Japan.
authors.forename: Tatsuya
authors.initials: T
authors.lastname: Higashi
keywords: Cancer; ROS-dependent apoptosis; ROS-independent apoptosis; chemotherapy; reactive oxygen species