Redox mechanism of levobupivacaine cytostatic effect on human prostate cancer cells.

Abstract

Anti-cancer effects of local anesthetics have been reported but the mode of action remains elusive. Here, we examined the bioenergetic and REDOX impact of levobupivacaine on human prostate cancer cells (DU145) and corresponding non-cancer primary human prostate cells (BHP). Levobupivacaine induced a combined inhibition of glycolysis and oxidative phosphorylation in cancer cells, resulting in a reduced cellular ATP production and consecutive bioenergetic crisis, along with reactive oxygen species generation. The dose-dependent inhibition of respiratory chain complex I activity by levobupivacaine explained the alteration of mitochondrial energy fluxes. Furthermore, the potency of levobupivacaine varied with glucose and oxygen availability as well as the cellular energy demand, in accordance with a bioenergetic anti-cancer mechanism. The levobupivacaine-induced bioenergetic crisis triggered cytostasis in prostate cancer cells as evidenced by a S-phase cell cycle arrest, without apoptosis induction. In DU145 cells, levobupivacaine also triggered the induction of autophagy and blockade of this process potentialized the anti-cancer effect of the local anesthetic. Therefore, our findings provide a better characterization of the REDOX mechanisms underpinning the anti-effect of levobupivacaine against human prostate cancer cells.

• Authors: Caroline Jose, Etienne Hebert-Chatelain, Nivea Dias Amoedo, Emmanuel Roche, Emilie Obre, Didier Lacombe, Hamid Reza Rezvani, Philippe Pourquier, Karine Nouette-Gaulain, Rodrigue Rossignol
• Journal: Redox biology (Redox Biol) Vol. 18 Pg. 33-42 (09 2018) ISSN: 2213-2317 [Electronic] Netherlands
• PMID: 29935387 (Publication Type: Journal Article, Research Support, Non-U.S. Gov't)
• Copyright: Copyright © 2018 The Authors. Published by Elsevier B.V. All rights reserved.

Chemical References

• Anesthetics, Local
• Antineoplastic Agents
• Reactive Oxygen Species
• Adenosine Triphosphate
• Levobupivacaine
• Bupivacaine

Topics

• Adenosine Triphosphate (metabolism)
• Anesthetics, Local (pharmacology)
• Antineoplastic Agents (pharmacology)
• Bupivacaine (analogs & derivatives, pharmacology)
• Cell Cycle Checkpoints (drug effects)
• Cell Line, Tumor
• Cell Respiration (drug effects)
• Cells, Cultured
• Energy Metabolism (drug effects)
• Glycolysis (drug effects)
• Humans
• Levobupivacaine
• Male
• Oxidation-Reduction (drug effects)
• Oxidative Phosphorylation (drug effects)
• Prostate (drug effects, metabolism)
• Prostatic Neoplasms (drug therapy, metabolism)
• Reactive Oxygen Species (metabolism)