Oxidative Phosphorylation as a Target to Arrest Malignant Neoplasias
Authors: Rodriguez-Enriquez, Sara; Carlos Gallardo-Perez, Juan; Marin-Hernandez, Alvaro; Luis Aguilar-Ponce, Jose; Ayerim Mandujano-Tinoco, Edna; Meneses, Abelardo; Moreno-Sanchez, Rafael
Source: Current Medicinal Chemistry, Volume 18, Number 21, July 2011 , pp. 3156-3167(12)
Publisher: Bentham Science Publishers
Abstract:Since Warburg proposed in 1956 that cancer cells exhibit increased glycolysis due to mitochondrial damage, numerous researchers have assumed that glycolysis is the predominant ATP supplier for cancer cell energy-dependent processes. However, chemotherapeutic strategies using glycolytic inhibitors have been unsuccessful in arresting tumor proliferation indicating that the Warburg hypothesis may not be applicable to all existing neoplasias. This review analyzes recent information on mitochondrial metabolism in several malignant neoplasias emphasizing that, although tumor cells maintain a high glycolytic rate, the principal ATP production may derive from active oxidative phosphorylation. Thus, anti-mitochondrial drug therapy may be an adequate adjuvant strategy to arrest proliferation of oxidative phosphorylation-dependent neoplasias.
Keywords: Anti-mitochondrial drugs; Krebs cycle; Warburg hypothesis; glycolysis; lipophilic cation drugs; mitochondrial substrate oxidation; multi-drug therapy; multi-site therapy; oxidative phosphorylation; respiratory inhibitors; uncouplers
Document Type: Research Article
Publication date: 2011-07-01
- Current Medicinal Chemistry covers all the latest and outstanding developments in medicinal chemistry and rational drug design. Each issue contains a series of timely in-depth reviews written by leaders in the field covering a range of the current topics in medicinal chemistry. Current Medicinal Chemistry is an essential journal for every medicinal chemist who wishes to be kept informed and up-to-date with the latest and most important developments.