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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.

journal_name

Biochem Biophys Res Commun

journal_title

Biochemical and biophysical research communications

authors

Qin JZ,Xin H,Nickoloff BJ

doi

10.1016/j.bbrc.2010.04.126

subject

Has Abstract

pub_date

2010-05-28 00:00:00

pages

495-500

issue

2

eissn

0006-291X

issn

1090-2104

pii

S0006-291X(10)00819-3

journal_volume

396

pub_type

杂志文章

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