title: Polyphenols as mitochondria-targeted anticancer drugs.
abstract: Mitochondria are the respiratory and energetic centers of the cell where multiple intra- and extracellular signal transduction pathways converge leading to dysfunction of those organelles and, consequently, apoptotic or/and necrotic cell death. Mitochondria-targeted anticancer drugs are referred to as mitocans; they have recently been classified by Neuzil et al. (2013) according to their molecular mode of action into: hexokinase inhibitors; mimickers of the Bcl-2 homology-3 (BH3) domains; thiol redox inhibitors; deregulators of voltage-dependent anionic channel (VDAC)/adenine nucleotide translocase (ANT) complex; electron redox chain-targeting agents; lipophilic cations targeting the mitochondrial inner membrane; tricarboxylic acid cycle-targeting agents; and mitochondrial DNA-targeting agents. Polyphenols of plant origin and their synthetic or semisynthetic derivatives exhibit pleiotropic biological activities, including the above-mentioned modes of action characteristic of mitocans. Some of them have already been tested in clinical trials. Gossypol has served as a lead compound for developing more efficient BH3 mimetics such as ABT-737 and its orally available structural analog ABT-263 (Navitoclax). Furthermore, mitochondriotropic derivatives of phenolic compounds such as quercetin and resveratrol have been synthesized and reported to efficiently induce cancer cell death in vitro.
authors.affiliation: Department of Biochemistry, Medical University of Lodz, Lodz, Poland.
authors.forename: Sylwia
authors.initials: S
authors.lastname: Gorlach
authors.affiliation: Department of Biochemistry, Medical University of Lodz, Lodz, Poland.
authors.forename: Jakub
authors.initials: J
authors.lastname: Fichna
authors.affiliation: Department of Biochemistry, Medical University of Lodz, Lodz, Poland. Electronic address: urszula.lewandowska@umed.lodz.pl.
authors.forename: Urszula
authors.initials: U
authors.lastname: Lewandowska
mesh_terms: D000818:Animals; D000970:Antineoplastic Agents / Q000494:pharmacology*; D002952:Citric Acid Cycle / Q000187:drug effects; D004272:DNA, Mitochondrial / Q000187:drug effects / Q000378:metabolism; D006072:Gossypol / Q000494:pharmacology; D006593:Hexokinase / Q000037:antagonists & inhibitors; D006801:Humans; D008928:Mitochondria / Q000187:drug effects* / Q000378:metabolism; D051336:Mitochondrial Membranes / Q000187:drug effects / Q000378:metabolism; D010084:Oxidation-Reduction / Q000187:drug effects; D059808:Polyphenols / Q000494:pharmacology*; D019253:Proto-Oncogene Proteins c-bcl-2 / Q000378:metabolism; D013449:Sulfonamides / Q000494:pharmacology; D050995:Voltage-Dependent Anion Channel 1 / Q000378:metabolism
chemical_list: C490492:ABT751; D000970:Antineoplastic Agents; D004272:DNA, Mitochondrial; D059808:Polyphenols; D019253:Proto-Oncogene Proteins c-bcl-2; D013449:Sulfonamides; C494762:VDAC1 protein, human; D050995:Voltage-Dependent Anion Channel 1; D006593:Hexokinase; D006072:Gossypol
keywords: Cancer; Chemoprevention; Derivative; Flavonoid