The environmental carcinogen benzo[a]pyrene induces a Warburg-like metabolic reprogramming dependent on NHE1 and associated with cell survival

• DOI: 10.1038/srep30776
• Publication Date: 2016-08-04T09:57:45Z
• Authors: Kévin Hardonnière; Elise Saunier; Anthony Lemarié; Morgane Fernier; Isabelle Gallais; Cécile Héliès-Tou...; Baharia Mograbi; Samantha Antonio; Paule Bénit; Pierre Rustin; Maxime Janin; Florence Habarou; Chris Ottolenghi; Marie-Thérèse Lav...; Chantal Benelli; Odile Sergent; Laurence Huc; Sylvie Bortoli; Dominique Lagadic...
• Keywords: Warburg Effect; Reprogramming

Abstract Cancer cells display alterations in many cellular processes. One core hallmark of cancer is the Warburg effect which a glycolytic reprogramming that allows to survive and proliferate. Although contributions environmental contaminants development are widely accepted, underlying mechanisms have be clarified. Benzo[a]pyrene (B[a]P), prototype polycyclic aromatic hydrocarbons, exhibits genotoxic carcinogenic effects it human carcinogen according International Agency for Research on Cancer. In addition triggering apoptotic signals, B[a]P may induce survival both likely involved promotion. We previously suggested B[a]P-induced mitochondrial dysfunctions, especially membrane hyperpolarization, might trigger cell signaling rat hepatic epithelial F258 cells. Here, we further characterized these dysfunctions by focusing energy metabolism. found promoted metabolic reprogramming. Cell respiration decreased lactate production increased. These changes were associated with tricarboxylic acid cycle involve dysfunction complex II. The shift relied activation Na + /H exchanger 1 (NHE1) appeared key feature related phenotype (epithelial-to-mesenchymal transition migration).