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Abstract Title:

Inhibition of mitochondrial respiration and rapid depletion of mitochondrial glutathione byβ-phenethyl isothiocyanate: mechanisms for anti-leukemia activity.

Abstract Source:

Antioxid Redox Signal. 2011 Dec 15 ;15(12):2911-21. Epub 2011 Sep 29. PMID: 21827296

Abstract Author(s):

Gang Chen, Zhao Chen, Yumin Hu, Peng Huang

Article Affiliation:

Gang Chen

Abstract:

AIMS: β-Phenethyl isothiocyanate (PEITC) is a natural product with potent anticancer activity against human leukemia cells including drug-resistant primary leukemia cells from patients. This study aimed at investigating the key mechanisms that contribute to the potent anti-leukemia activity of PEITC andat evaluating its therapeutic potential.

RESULTS: Our study showed that PEITC caused a rapid depletion of mitochondrial glutathione (GSH) and a significant elevation of reactive oxygen species (ROS) and nitric oxide, and induced a disruption of the mitochondrial electron transport complex I manifested by an early degradation of NADH dehydrogenase Fe-S protein-3 and a significant suppression of mitochondrial respiration. Using biochemical and pharmacological approaches, we further showed that inhibition of mitochondrial respiration alone by rotenone caused only a moderate cytotoxicity in leukemia cells, whereas a combination of respiratory inhibition and an ROS-generating agent exhibited a synergistic effect against leukemia and lymphoma cells.

INNOVATION AND CONCLUSION: Although PEITC is a reactive compound and might have multiple mechanisms of action, we showed that a rapid depletion of GSH and inhibition of mitochondrial respiration are two important early events that induced synergistic cytotoxicity in leukemia cells. These findings not only suggest that PEITC is a promising compound for potential use in leukemia treatment, but also provide a basis for developing new therapeutic strategies to effectively kill leukemia cells by using a novel combination to modulate ROS and inhibit mitochondrial respiration.

Study Type : In Vitro Study

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Sayer Ji
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