Mitochondrial Peroxiredoxin III is a Potential Target for Cancer Therapy

We review accumulating evidence suggesting that mitochondrial oxidative stress is involved in cancer, and discuss the role of the mitochondrial Prx III antioxidant system as a potential target for cancer therapy

In-Sung Song; Hyoung-Kyu Kim; Seung-Hun Jeong; Sung-Ryul Lee; Nari Kim; Byoung Doo Rhee; Kyung Soo Ko; Jin Han

2011

Scholarcy highlights

  • National Research Laboratory for Mitochondrial Signaling, Department of Physiology, College of Medicine, Cardiovascular and Metabolic Disease Center, Inje University, Busan 614-7-5, Korea; Tel.: +82-51-890-6727; Fax: +82-51-894-5714
  • Mitochondrial abnormalities occur in various diseases, including cardiovascular, neurodegenerative, metabolic diseases, and cancer
  • The increase in intrinsic ΔΨm correlates with increased malignancy, suggesting that cytotoxic agents that permeabilize the mitochondrial membrane, such as compounds that induce the overproduction of reactive oxygen species, are effective anticancer drugs in cancer cells
  • Many reports have claimed an association between alterations in the protein level of Prx isoforms. Such Prxs serve divergent functions, such as protecting cells against oxidative stress, regulating cell signaling associated with H2O2, and influencing cell differentiation and proliferation, immune responses, and apoptosis Recent studies reported elevated expression of Prx I in several human cancers, including non-small cell lung cancer, oral cancer, breast cancer, and liver cancer
  • Its specific localization to mitochondria suggests that Prx III, together with its mitochondrion-specific electron suppliers Trx2 and Trx reductase 2, might provide a primary line of defense against H2O2 produced by the mitochondrial respiratory chain, as SOD2 does against the superoxide radical
  • Trx-related antioxidant system composed of Trx2, TrxR2, and Prx III has been closely associated with the regulation of apoptosis and the redox control of mitochondrial permeability transition pores for the release of cytochrome c
  • A comprehensive understanding of mitochondrial biology in cancer cells and the interaction between cellular metabolism and drug action is essential in the development of mitochondrion-targeted agents for cancer treatment

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