Abstract
Tumours exhibit higher basal levels of reactive oxygen species (ROS) and altered redox environment compared to normal cells. Excessive level of ROS can be toxic to these cells, thus they become more vulnerable to damage by further ROS insults induced by pharmacological agents. However, the upregulation of antioxidant capacity in adaptation to intrinsic oxidative stress in cancer cells can confer drug resistance. Therefore, abrogation of such drugresistant mechanisms by redox modulation could have significant therapeutic implications. Many redox-modulating agents have been developed. The redox-active system epitomised by ascorbate-driven quinone redox cycling, and the group of redox-silent vitamin E analogues represented by α-tocopheryl succinate have been shown to induce selective cancer cell death in different types of cancer. These compounds synergistically act by destabilising organelles like mitochondria, unleashing their apoptogenic potential, which results in efficient death of malignant cells and suppression of tumour growth. Consistent with this notion, clinical trials that aim to examine the therapeutic performance of novel redoxmodulating drugs in cancer patients are currently under way.
Keywords: Apoptosis, autophagy, redox-active agents, redox-silent agent, ROS-based cancer therapy, vitamin E analogues.
Current Medicinal Chemistry
Title:Redox-active and Redox-silent Compounds: Synergistic Therapeutics in Cancer
Volume: 22 Issue: 5
Author(s): M. Tomasetti, L. Santarelli, R. Alleva, Lan-Feng Dong and J. Neuzil
Affiliation:
Keywords: Apoptosis, autophagy, redox-active agents, redox-silent agent, ROS-based cancer therapy, vitamin E analogues.
Abstract: Tumours exhibit higher basal levels of reactive oxygen species (ROS) and altered redox environment compared to normal cells. Excessive level of ROS can be toxic to these cells, thus they become more vulnerable to damage by further ROS insults induced by pharmacological agents. However, the upregulation of antioxidant capacity in adaptation to intrinsic oxidative stress in cancer cells can confer drug resistance. Therefore, abrogation of such drugresistant mechanisms by redox modulation could have significant therapeutic implications. Many redox-modulating agents have been developed. The redox-active system epitomised by ascorbate-driven quinone redox cycling, and the group of redox-silent vitamin E analogues represented by α-tocopheryl succinate have been shown to induce selective cancer cell death in different types of cancer. These compounds synergistically act by destabilising organelles like mitochondria, unleashing their apoptogenic potential, which results in efficient death of malignant cells and suppression of tumour growth. Consistent with this notion, clinical trials that aim to examine the therapeutic performance of novel redoxmodulating drugs in cancer patients are currently under way.
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Cite this article as:
Tomasetti M., Santarelli L., Alleva R., Dong Lan-Feng and Neuzil J., Redox-active and Redox-silent Compounds: Synergistic Therapeutics in Cancer, Current Medicinal Chemistry 2015; 22 (5) . https://dx.doi.org/10.2174/0929867321666140915142219
DOI https://dx.doi.org/10.2174/0929867321666140915142219 |
Print ISSN 0929-8673 |
Publisher Name Bentham Science Publisher |
Online ISSN 1875-533X |
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