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The differential role of reactive oxygen species in early and late stages of cancer

Abstract : The large doses of vitamins C and E and beta-carotene used to reduce reactive oxygen species (ROS) production and oxidative damages in cancerous tissue have produced disappointing and contradictory results. This therapeutic conundrum was attributed to the double-faced role of ROS, notably, their ability to induce either proliferation or apoptosis of cancer cells. However, for a ROS-inhibitory approach to be effective, it must target ROS when they induce proliferation rather than apoptosis. On the basis of recent advances in redox biology, this review underlined a differential regulation of prooxidant and antioxidant system, respective to the stage of cancer. At early precancerous and neoplastic stages, antioxidant activity decreases and ROS appear to promote cancer initiation via inducing oxidative damage and base pair substitution mutations in prooncogenes and tumor suppressor genes, such as RAS and TP53, respectively. Whereas in late stages of cancer progression, tumor cells escape apoptosis by producing high levels of intracellular antioxidants, like NADPH and GSH, via the pentose phosphate pathway to buffer the excessive production of ROS and related intratumor oxidative injuries. Therefore, antioxidants should be prohibited in patients with advanced stages of cancer and/or undergoing anticancer therapies. Interestingly, the biochemical and biophysical properties of some polyphenols allow them to selectively recognize tumor cells. This characteristic was exploited to design and deliver nanoparticles coated with low doses of polyphenols and containing chemotherapeutic drugs into tumor-bearing animals. First results are encouraging, which may revolutionize the conventional use of antioxidants in cancer.
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https://hal-univ-rennes1.archives-ouvertes.fr/hal-01671803
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Submitted on : Friday, December 22, 2017 - 4:13:22 PM
Last modification on : Monday, February 11, 2019 - 11:36:36 AM

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Mohamad Assi. The differential role of reactive oxygen species in early and late stages of cancer. AJP - Regulatory, Integrative and Comparative Physiology, American Physiological Society, 2017, 313 (6), pp.R646-R653. ⟨10.1152/ajpregu.00247.2017⟩. ⟨hal-01671803⟩

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