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J Bioenerg Biomembr. 2012 Feb;44(1):81-90. doi: 10.1007/s10863-012-9415-6. Epub 2012 Feb 10.

Experimental results using 3-bromopyruvate in mesothelioma: in vitro and in vivo studies.

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Service de Chirurgie Thoracique, Centre Hospitalier Universitaire de Caen Basse-Normandie, Avenue de la Côte de Nacre, Caen 14000, France.

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  • J Bioenerg Biomembr. 2012 Dec;44(6):673. Philippe, Icard [corrected to Icard, Philippe]; Xiao-Dong, Zhang [corrected to Zhang, Xiao-Dong]; Edwige, Lemoisson [corrected to Lemoisson, Edwige]; Marie-Hélène, Louis [corrected to Louis, Marie-Hélène]; Stéphane, Allouche [corrected to Allouche, Stéphane]; Hubert, Lincet [corrected to Lincet, Hubert]; Laurent, Poulain [corrected to Poulain, Laurent].


Over many years we have taken advantage of the special metabolism of cancer cells involving an increased consumption of glucose associated with lactic acid production even in the presence of oxygen, a phenomenon referred to as the "Warburg effect", to counteract cancer cell growth. We have tested 3-bromopyruvate (3-BrPA), an inhibitor of pyruvate-associated reactions. Firstly, we tested this agent, in vitro, in two mesothelioma cell lines. Cellular response would appear to depend on the mode of administration (immediately or 24 h after seeding). Depending on the line, 3-BrPA induced a cytostatic or cytotoxic effect. This effect was accompanied by cell death induction even in cells highly refractory to cisplatin. Mitochondrial apoptotic death appeared to involve both lines; however, a different death pathway such as necrosis cannot be excluded. Interestingly, 3-BrPA leads to a diminution of the expression of the anti-apotptoic protein Mcl-1. We then tested 3-BrPA in vivo. Survival of nude mice bearing human mesothelioma was significantly prolonged (p < 0.0001). Toxicity and clinical studies should be performed to test 3- BrPA as local therapy for patients suffering from pleural or peritoneal mesothelioma. Association with cisplatin should be particularly considered.

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