Redox-active and Redox-silent Compounds: Synergistic Therapeutics in Cancer

0446855 - BTÚ 2016 RIV NL eng J - Journal Article
Tomasetti, M. - Santarelli, L. - Alleva, R. - Dong, L.F. - Neužil, Jiří
Redox-active and Redox-silent Compounds: Synergistic Therapeutics in Cancer.
Current Medicinal Chemistry. Roč. 22, č. 5 (2015), s. 552-568. ISSN 0929-8673. E-ISSN 1875-533X
R&D Projects: GA MŠMT(CZ) ED1.1.00/02.0109
Institutional support: RVO:86652036
Keywords : Apoptosis * autophagy * redox-active agents
Subject RIV: EB - Genetics ; Molecular Biology
Impact factor: 3.455, year: 2015

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 drug-resistant 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 alpha-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 redox-modulating drugs in cancer patients are currently under way
Permanent Link: http://hdl.handle.net/11104/0248837