Novel therapy for malignant pleural mesothelioma based on anti-energetic effect: an experimental study using 3-Bromopyruvate on nude mice.
BACKGROUND
Most cancer cells exhibit increased anaerobic glycolysis and use this metabolic pathway for the generation of ATP as a main source of energy. This impaired metabolism of glucose, leading to the secretion of lactic acid even in the presence of oxygen, is named the Warburg effect. Because cancer cells are partly or mainly dependent on such a pathway to generate ATP, inhibition of glycolysis may slow down the proliferation or kill cells.


METHODS
The effect of 3-Bromopyruvate (3-BrPA) alone or associated to cisplatin on nude mice presenting intraperitoneal carcinomatosis developed after intraperitoneal injection of human mesothelioma cells (MSTO-211H) was investigated.


RESULTS
3-BrPA significantly prolonged survival of animals. Combined with cisplatin, it demonstrated significant benefit on survival whereas cisplatin alone had no or a mild effect.


CONCLUSIONS
3-BrPA may thus constitute an interesting novel anticancer drug that could be tested in humans.
Zhang
Xiaodong
X
Anticancer Center Francois BACLESSE, Caen, France.
Varin
Emilie
E
Briand
Mélanie
M
Allouche
Stéphane
S
Heutte
Natacha
N
Schwartz
Laurent
L
Poulain
Laurent
L
Icard
Philippe
P
D000818:Animals; D002945:Cisplatin / Q000494:pharmacology; D004734:Energy Metabolism; D004791:Enzyme Inhibitors / Q000494:pharmacology*; D005260:Female; D006801:Humans; D008654:Mesothelioma / Q000188:drug therapy* / Q000473:pathology; D051379:Mice; D008819:Mice, Nude; D008928:Mitochondria / Q000187:drug effects / Q000378:metabolism; D010101:Oxygen Consumption / Q000187:drug effects*; D010534:Peritoneal Neoplasms / Q000188:drug therapy* / Q000556:secondary; D010997:Pleural Neoplasms / Q000188:drug therapy* / Q000473:pathology; D011768:Pyruvate Dehydrogenase Complex / Q000037:antagonists & inhibitors; D011773:Pyruvates / Q000494:pharmacology*; D014407:Tumor Cells, Cultured
D004791:Enzyme Inhibitors; D011768:Pyruvate Dehydrogenase Complex; D011773:Pyruvates; C017092:bromopyruvate; D002945:Cisplatin