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BioMed Research International
Volume 2014, Article ID 926729, 10 pages
http://dx.doi.org/10.1155/2014/926729
Review Article

Autophagy, Warburg, and Warburg Reverse Effects in Human Cancer

1Institute of Biochemistry and Molecular Medicine, National Council for Scientific and Technological Research, School of Pharmacy and Biochemistry, University of Buenos Aires, Junin 956 p5, 1113 Buenos Aires, Argentina
2Department of Pharmacology, CEMIC University Institute, 1113 Buenos Aires, Argentina

Received 23 April 2014; Accepted 24 July 2014; Published 12 August 2014

Academic Editor: Genichiro Ishii

Copyright © 2014 Claudio D. Gonzalez et al. This is an open access article distributed under the Creative Commons Attribution License, which permits unrestricted use, distribution, and reproduction in any medium, provided the original work is properly cited.

Abstract

Autophagy is a highly regulated-cell pathway for degrading long-lived proteins as well as for clearing cytoplasmic organelles. Autophagy is a key contributor to cellular homeostasis and metabolism. Warburg hypothesized that cancer growth is frequently associated with a deviation of a set of energy generation mechanisms to a nonoxidative breakdown of glucose. This cellular phenomenon seems to rely on a respiratory impairment, linked to mitochondrial dysfunction. This mitochondrial dysfunction results in a switch to anaerobic glycolysis. It has been recently suggested that epithelial cancer cells may induce the Warburg effect in neighboring stromal fibroblasts in which autophagy was activated. These series of observations drove to the proposal of a putative reverse Warburg effect of pathophysiological relevance for, at least, some tumor phenotypes. In this review we introduce the autophagy process and its regulation and its selective pathways and role in cancer cell metabolism. We define and describe the Warburg effect and the newly suggested “reverse” hypothesis. We also discuss the potential value of modulating autophagy with several pharmacological agents able to modify the Warburg effect. The association of the Warburg effect in cancer and stromal cells to tumor-related autophagy may be of relevance for further development of experimental therapeutics as well as for cancer prevention.