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:Griffith University, Southport, Qld 4222, Australia.
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.
