skip to main content
OSTI.GOV title logo U.S. Department of Energy
Office of Scientific and Technical Information

Title: 3-Bromopyruvate induces necrotic cell death in sensitive melanoma cell lines

Abstract

Clinicians successfully utilize high uptake of radiolabeled glucose via PET scanning to localize metastases in melanoma patients. To take advantage of this altered metabolome, 3-bromopyruvate (BrPA) was used to overcome the notorious resistance of melanoma to cell death. Using four melanoma cell lines, BrPA triggered caspase independent necrosis in two lines, whilst the other two lines were resistant to killing. Mechanistically, sensitive cells differed from resistant cells by; constitutively lower levels of glutathione, reduction of glutathione by BrPA only in sensitive cells; increased superoxide anion reactive oxygen species, loss of outer mitochondrial membrane permeability, and rapid ATP depletion. Sensitive cell killing was blocked by N-acetylcysteine or glutathione. When glutathione levels were reduced in resistant cell lines, they became sensitive to killing by BrPA. Taken together, these results identify a metabolic-based Achilles' heel in melanoma cells to be exploited by use of BrPA. Future pre-clinical and clinical trials are warranted to translate these results into improved patient care for individuals suffering from metastatic melanoma.

Authors:
;  [1];  [1]
  1. Oncology Institute, Cardinal Bernardin Cancer Center, Loyola University of Chicago Medical Center (United States)
Publication Date:
OSTI Identifier:
22202623
Resource Type:
Journal Article
Resource Relation:
Journal Name: Biochemical and Biophysical Research Communications; Journal Volume: 396; Journal Issue: 2; Other Information: Copyright (c) 2010 Elsevier Science B.V., Amsterdam, The Netherlands, All rights reserved.; Country of input: International Atomic Energy Agency (IAEA)
Country of Publication:
United States
Language:
English
Subject:
60 APPLIED LIFE SCIENCES; ANIONS; APOPTOSIS; ATP; CELL KILLING; CLINICAL TRIALS; GLUCOSE; GLUTATHIONE; MELANOMAS; METASTASES; MITOCHONDRIA; NECROSIS; PATIENTS; PERMEABILITY; POSITRON COMPUTED TOMOGRAPHY

Citation Formats

Qin, J.-Z., Xin, H., and Nickoloff, B.J., E-mail: bnickol@lumc.edu. 3-Bromopyruvate induces necrotic cell death in sensitive melanoma cell lines. United States: N. p., 2010. Web. doi:10.1016/J.BBRC.2010.04.126.
Qin, J.-Z., Xin, H., & Nickoloff, B.J., E-mail: bnickol@lumc.edu. 3-Bromopyruvate induces necrotic cell death in sensitive melanoma cell lines. United States. doi:10.1016/J.BBRC.2010.04.126.
Qin, J.-Z., Xin, H., and Nickoloff, B.J., E-mail: bnickol@lumc.edu. Fri . "3-Bromopyruvate induces necrotic cell death in sensitive melanoma cell lines". United States. doi:10.1016/J.BBRC.2010.04.126.
@article{osti_22202623,
title = {3-Bromopyruvate induces necrotic cell death in sensitive melanoma cell lines},
author = {Qin, J.-Z. and Xin, H. and Nickoloff, B.J., E-mail: bnickol@lumc.edu},
abstractNote = {Clinicians successfully utilize high uptake of radiolabeled glucose via PET scanning to localize metastases in melanoma patients. To take advantage of this altered metabolome, 3-bromopyruvate (BrPA) was used to overcome the notorious resistance of melanoma to cell death. Using four melanoma cell lines, BrPA triggered caspase independent necrosis in two lines, whilst the other two lines were resistant to killing. Mechanistically, sensitive cells differed from resistant cells by; constitutively lower levels of glutathione, reduction of glutathione by BrPA only in sensitive cells; increased superoxide anion reactive oxygen species, loss of outer mitochondrial membrane permeability, and rapid ATP depletion. Sensitive cell killing was blocked by N-acetylcysteine or glutathione. When glutathione levels were reduced in resistant cell lines, they became sensitive to killing by BrPA. Taken together, these results identify a metabolic-based Achilles' heel in melanoma cells to be exploited by use of BrPA. Future pre-clinical and clinical trials are warranted to translate these results into improved patient care for individuals suffering from metastatic melanoma.},
doi = {10.1016/J.BBRC.2010.04.126},
journal = {Biochemical and Biophysical Research Communications},
number = 2,
volume = 396,
place = {United States},
year = {Fri May 28 00:00:00 EDT 2010},
month = {Fri May 28 00:00:00 EDT 2010}
}