Dissemin is shutting down on January 1st, 2025

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Wiley Open Access, Molecular Oncology, 1(2), p. 94-101, 2008

DOI: 10.1016/j.molonc.2008.01.003

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3‐Bromopyruvate as inhibitor of tumour cell energy metabolism and chemopotentiator of platinum drugs

Journal article published in 2008 by Linda Strandberg Ihrlund, Emma Hernlund, Omar Khan ORCID, Maria C. Shoshan
This paper is made freely available by the publisher.
This paper is made freely available by the publisher.

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Abstract

Tumour cells depend on aerobic glycolysis for adenosine triphosphate (ATP) production, making energy metabolism an interesting therapeutic target. 3-Bromopyruvate (BP) has been shown by others to inhibit hexokinase and eradicate mouse hepatocarcinomas. We report that similar to the glycolysis inhibitor 2-deoxyglucose (DG), BP rapidly decreased cellular ATP within hours, but unlike DG, BP concomitantly induced mitochondrial depolarization without affecting levels of reducing equivalents. Over 24h, and at equitoxic doses, DG reduced glucose consumption more than did BP. The observed BP-induced loss of ATP is therefore largely due to mitochondrial effects. Cell death induced over 24h by BP, but not DG, was blocked by N-acetylcysteine, indicating involvement of reactive oxygen species. BP-induced cytotoxicity was independent of p53. When combined with cisplatin or oxaliplatin, BP led to massive cell death. The anti-proliferative effects of low-dose platinum were strikingly potentiated also in resistant p53-deficient cells. Together with the reported lack of toxicity, this indicates the potential of BP as a clinical chemopotentiating agent.