Mitochondrial complex II, a novel target for anti-cancer agents

Abstract

With the arrival of the third millennium, in spite of unprecedented progress in molecular medicine, cancer remains as untamed as ever. The complexity of tumours, dictating the potential response of cancer cells to anti-cancer agents, has been recently highlighted in a landmark paper by Weinberg and Hanahan on hallmarks of cancer [1]. Together with the recently published papers on the complexity of tumours in patients and even within the same tumour (see below), the cure for this pathology seems to be an elusive goal. Indisputably, the strategy ought to be changed, searching for targets that are generally invariant across the landscape of neoplastic diseases. One such target appears to be the mitochondrial complex II (CII) of the electron transfer chain, a recent focus of research. We document and highlight this particularly intriguing target in this review paper and give examples of drugs that use CII as their molecular target. This article is part of a Special Issue entitled: Respiratory complex II: Role in cellular physiology and disease.

Red LED Photobiomodulates the Metabolic Activity of Odontoblast-Like Cells

“…It is well known that SDH consists in a protein that belongs to the complex II of the cellular respiratory chain. This protein, therefore, acts within the electron transference catalysis (24), which determines the physiological ROS production (25). Therefore, the present results reinforce the hypothesis that the light's mechanism of action is by mitochondrial pathway.…”

2-Methoxyestradiol Affects Mitochondrial Biogenesis Pathway and Succinate Dehydrogenase Complex Flavoprotein Subunit A in Osteosarcoma Cancer Cells

“…Despite the dual activity of SDH in cancer formation and/or anticancer effects, mutations in SDHA gene are also associated with Leigh syndrome, neuronal cell death and/or some form of progressive neurodegenerative disease (59,63). The association of SDHA deficiency with neurodegeneration may explain the plausible neurotoxic effects of 2-ME previously observed by us in hippocampal experimental model (24,25,68).…”

“…Mitochondrial SDH, also known as Complex II or succinate: ubiquinone oxidoreductase (SQR), contains four nuclear encoded subunits: SDH A-D (59). SDH has the unique characteristic of being the component that links the Krebs cycle and the electron transport chain.…”

The Assembly Factor SDHAF2 Is Dispensable for Flavination of the Catalytic Subunit of Mitochondrial Complex II in Breast Cancer Cells

“…CII, also known as succinate dehydrogenase (SDH), contains four subunits: the hydrophilic SDHA (a flavoprotein) and SDHB (an iron-sulfur protein), plus the hydrophobic SDHC and SDHD (1,2). CII is an important source of reactive oxygen species in mitochondria (3)(4)(5)(6) and serves as a critical step in both the tricarboxylic acid (TCA) cycle and OXPHOS, linking these two essential cellular pathways (1,2,(7)(8)(9). In the TCA cycle, SDH oxidizes succinate to fumarate (SDH activity) in a reaction that depends on the presence of FAD in the active site of SDHA (1,2,8,10).…”