Saturday, January 20, 2007

I want this article, grrr

The New Scientist reported about a cure for most cancers by a dichloroacetate as a magic bullet and mentions the Michelakis group report in the current «Cancer Cell». The article isn't e-published on PudMed yet and this drives me up the walls! I want to read the details and not the populist New Scientist yada-yada.

The PubMed-abstract:

A mitochondria-k(+) channel axis is suppressed in cancer and its normalization promotes apoptosis and inhibits cancer growth.

Bonnet S, Archer SL, Allalunis-Turner J, Haromy A, Beaulieu C, Thompson R, Lee CT, Lopaschuk GD, Puttagunta L, Bonnet S, Harry G, Hashimoto K, Porter CJ, Andrade MA, Thebaud B, Michelakis ED.

Pulmonary Hypertension Program and Vascular Biology Group, University of Alberta, Edmonton, AB T6G 2B7, Canada.

The unique metabolic profile of cancer (aerobic glycolysis) might confer apoptosis resistance and be therapeutically targeted. Compared to normal cells, several human cancers have high mitochondrial membrane potential (DeltaPsim) and low expression of the K(+) channel Kv1.5, both contributing to apoptosis resistance. Dichloroacetate (DCA) inhibits mitochondrial pyruvate dehydrogenase kinase (PDK), shifts metabolism from glycolysis to glucose oxidation, decreases DeltaPsim, increases mitochondrial H(2)O(2), and activates Kv channels in all cancer, but not normal, cells; DCA upregulates Kv1.5 by an NFAT1-dependent mechanism. DCA induces apoptosis, decreases proliferation, and inhibits tumor growth, without apparent toxicity. Molecular inhibition of PDK2 by siRNA mimics DCA. The mitochondria-NFAT-Kv axis and PDK are important therapeutic targets in cancer; the orally available DCA is a promising selective anticancer agent.

Update: The article is online on ScienceDirect.

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