Targeting malignant mitochondria with therapeutic peptides

Department of Pharmacology & Toxicology, College of Pharmacy, University of Utah, Salt Lake City, UT 84108, USA.
Therapeutic delivery 08/2012; 3(8):961-79. DOI: 10.4155/tde.12.75
Source: PubMed

ABSTRACT The current status of peptides that target the mitochondria in the context of cancer is the focus of this review. Chemotherapy and radiotherapy used to kill tumor cells are principally mediated by the process of apoptosis that is governed by the mitochondria. The failure of anticancer therapy often resides at the level of the mitochondria. Therefore, the mitochondrion is a key pharmacological target in cancer due to many of the differences that arise between malignant and healthy cells at the level of this ubiquitous organelle. Additionally, targeting the characteristics of malignant mitochondira often rely on disruption of protein--protein interactions that are not generally amenable to small molecules. We discuss anticancer peptides that intersect with pathological changes in the mitochondrion.

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    • "One of the key differences between malignant and healthy mitochondria may be the high mitochondrial membrane potential (Δψm) [21]. Even slight gains in Δψm have been proposed to confer to cationic agents a greater targeting of mitochondrial membranes and, consequently, better membrane permeabilization and cell death induction in cancer cells [22]. To further provide insight into the interaction of KLA with mitochondrial membrane lipids, a biophysical approach has been chosen (3.3 below). "
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