Reprofiling a classical anthelmintic, pyrvinium pamoate, as an anti-cancer drug targeting mitochondrial respiration
Open Access
- 1 January 2012
- journal article
- Published by Frontiers Media SA in Frontiers in Oncology
- Vol. 2, 137
- https://doi.org/10.3389/fonc.2012.00137
Abstract
Pyrvinium pamoate (PP) is an FDA-approved classical anthelmintic, but is now attracting particular attention as an anti-cancer drug after recent findings of its potent cytotoxicity against various cancer cell lines only during glucose starvation, as well as its anti-tumor activity against hypovascular pancreatic cancer cells transplanted in mice. The molecular mechanisms by which PP promotes such preferential toxicity against cancer cells are currently under extensive investigation. PP suppressed the NADH-fumarate reductase system that mediates a reverse reaction of the mitochondrial electron-transport chain complex II in anaerobic organisms such as parasitic helminthes or mammalian cells under tumor microenvironment-mimicking hypoglycemic/hypoxic conditions, thereby inhibiting efficient ATP production. PP also inhibited the unfolded protein response induced by glucose starvation, thereby inhibiting the proliferation of pancreatic cancer cells. Even under normoglycemic/normoxic conditions, PP suppressed the mitochondrial electron-transport chain complex I and thereby STAT3, inhibiting the proliferation of myeloma/erythroleukemia cells. Here, we review accumulating knowledge on its working mechanisms and evaluate PP as a novel anti-cancer drug that targets mitochondrial respiration.Keywords
This publication has 27 references indexed in Scilit:
- Pyrvinium pamoate inhibits proliferation of myeloma/erythroleukemia cells by suppressing mitochondrial respiratory complex I and STAT3Cancer Letters, 2012
- Metabolic symbiosis in cancer: Refocusing the Warburg lensMolecular Carcinogenesis, 2012
- Protein Kinase CK1α Regulates Erythrocyte SurvivalCellular Physiology and Biochemistry, 2012
- Small-molecule inhibition of Wnt signaling through activation of casein kinase 1αNature Chemical Biology, 2010
- Regulation of succinate-ubiquinone reductase and fumarate reductase activities in human complex II by phosphorylation of its flavoprotein subunitProceedings of the Japan Academy, Series B, 2009
- The cell death regulator GRIM-19 is an inhibitor of signal transducer and activator of transcription 3Proceedings of the National Academy of Sciences of the United States of America, 2003
- The unfolded protein responseJournal of Cell Science, 2003
- Biological consequences of tumor hypoxia.2001
- Metabolic stress and altered glucose transport: activation of AMP-activated protein kinase as a unifying coupling mechanism.Diabetes, 2000
- On Respiratory Impairment in Cancer CellsScience, 1956