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. 2016 Aug;28(4):383-96.
doi: 10.21147/j.issn.1000-9604.2016.04.01.

Overproduction of reactive oxygen species - obligatory or not for induction of apoptosis by anticancer drugs

Donika Ivanova  1 , Zhivko Zhelev  2 , Ichio Aoki  3 , Rumiana Bakalova  4 , Tatsuya Higashi  3
Affiliations

Overproduction of reactive oxygen species - obligatory or not for induction of apoptosis by anticancer drugs

Donika Ivanova et al. Chin J Cancer Res. 2016 Aug.

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.

Keywords: Cancer; ROS-dependent apoptosis; ROS-independent apoptosis; chemotherapy; reactive oxygen species.

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Conflict of interest statement

The authors have no conflicts of interest to declare.

Figures

1
1
Main endogenous triggers of ROS and consequences of their interaction with antioxidant systems. Changes in the expression and status of antioxidant systems may cause different cell responses, from apoptosis to adaptation, and uncontrolled proliferation.
2
2
Main pathways (intrinsic and extrinsic) for induction of apoptosis in cells. Bax, Bak. Bad, Bok, etc. are pro-apoptotic proteins; Bcl-2, Bcl-W, Bcl-xL, etc. are anti-apoptotic proteins; APAF1, apoptotic protease activating factor 1; DISC, death-inducing signaling complex.
3
3
Role of anticancer drugs in ROS-dependent and ROS-independent induction of apoptosis.
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