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

Author(s): M. Tomasetti, L. Santarelli, R. Alleva, Lan-Feng Dong, J. Neuzil.

Journal Name: Current Medicinal Chemistry

Volume 22 , Issue 5 , 2015

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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.

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Article Details

VOLUME: 22
ISSUE: 5
Year: 2015
Page: [552 - 568]
Pages: 17
DOI: 10.2174/0929867321666140915142219
Price: $58

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