Reactive oxygen species (ROS) are highly reactive chemicals which contain oxygen radicals. Hypochlorous acid, peroxides, superoxide, singlet oxygen, alpha-oxygen and hydroxyl radicals are the major examples of ROS, which are familiar to persons from many walks of life as they are used in many domestic and industrial processes. ROS are naturally produced during a variety of biochemical reactions within the cell organelles such as the endoplasmic reticulum, mitochondria and peroxisomes. ROS are also formed as a byproduct of the normal metabolism of oxygen. The production of ROS can be induced by various factors such as heavy metals, tobacco, smoke, drugs, xenobiotics, pollutants and radiation. From various experimental studies, it is reported that ROS acts as either tumor suppressing or tumor promoting agent. The elevated level of ROS can arrest the growth of tumor through the persistent increase in cell cycle inhibition. The increased level of ROS can induce apoptosis by both intrinsic and extrinsic pathways. ROS is considered to be tumor suppressing agent as the production of ROS is due to use of most of the chemotherapeutic agents in order to activate the cell death. The cytotoxic effect of ROS provides impetus towards apoptosis but in higher levels, ROS can cause initiation of malignancy that leads to uncontrolled cell death in cancer cells. Whereas, some species of ROS can influence various activities at cellular level that include cell proliferation. This recent review, published in Anti-Cancer Agents in Medicinal Chemistry explains the significance of ROS in cancer therapy.
Scientific reports suggest that ROS may promote either cell proliferation or cell death depending on the intensity or location of the oxidative burst and the activity of the antioxidant system. The ability of ROS to stimulate cell growth or cell death mainly depends on the intensity or duration of redox signals and defense mechanisms of antioxidants. The existing anti-cancer drugs exert harmful effects on normal cells which are partially activated by ROS. These species exert reverse cellular effects by promoting either cell proliferation and tumor progression or cell death. ROS act as "double edged sword" by acting not only as disease inducers or sustainers but also act as therapeutic weapons in cancer cells. The increased level of ROS in mitochondria is found to induce cell proliferation, cell survival, cell migration, and epithelial-mesenchymal transition through mitogen-activated protein kinase (MAPK) and Ras-ERK activation.
With these intracellular effects in view, various reactive oxygen species can be applied therapeutically for the treatment of different types of cancer cells. Novel therapeutic approaches of anti-cancer drugs are based on formation ROS or modulation of antioxidant mechanisms. By being able to differentiate between normal and cancer cells through the use of molecular signals researchers can target cancer cells for destruction in vivo. In spite of the current techniques of ROS signaling in cancer biology, the dual nature of ROS is still a great challenge in cancer therapies that target to ROS. The understanding of properties of ROS as major factor in signaling pathways may offer hope in the clinic for safer and effective pharmacological anti-cancer interventions in the future.
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aRoland Institute of Pharmaceutical Sciences (Biju Patnaik University of Technology Nodal Centre of Research), Berhampur-760010, Odisha, India;
bDepartment of Mathematics and Natural Sciences, College of Sciences and Human Studies, Prince Mohammad Bin Fahd University, Al Khobar, Kingdom of Saudi Arabia,
cCSIR-Central Scientific Instruments Organization, Chandigarh, India;
dDepartment of Chemistry, MRK Educational Institutions, IGU Rewari, Haryana, India.
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Anti-Cancer Agents in Medicinal Chemistry