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Reversing the Warburg Effect as a Treatment for Glioblastoma.

Al's Comment:

 The "Warburg effect"  is an observation that cancer cells usually metabolize glucose differently than normal cells. These researchers are trying to change the process back to how it is in normal cells using a relatively simple chemical.  This is only in the test tube now and more research is needed before we can tell if it works in people.


Posted on: 02/16/2013

J Biol Chem. 2013 Feb 13. [Epub ahead of print]
Reversing the Warburg Effect as a Treatment for Glioblastoma.

For full text of article click here


Poteet E, Choudhury GR, Winters A, Li W, Ryou MG, Liu R, Tang L, Ghorpade A, Wen Y, Yuan F, Keir ST, Yan H, Bigner DD, Simpkins JW, Yang SH.
Source
University of North Texas Health Science Center, United States;
Abstract
Glioblastoma multiforme (GBM), like most cancers, possesses a unique bioenergetic state of aerobic glycolysis known as the Warburg Effect. Here, we documented that methylene blue (MB) reverses the Warburg effect evidenced by the increasing of oxygen consumption and reduction of lactate production in GBM cell lines. MB decreases GBM cell proliferation and halts the cell cycle in S phase. Through activation of AMP- activated protein kinase (AMPK), MB inactivates downstream acetyl-CoA carboxylase and decreases cyclin expression. Structure-activity relationship analysis demonstrated that toluidine blue O, an MB derivative with similar bioenergetic actions, exerts similar action in GBM cell proliferation. In contrast, two other MB derivatives, 2-chlorophenothiazine and promethazine, exert no effect on cellular bioenergetics and do not inhibit GBM cell proliferation. MB inhibits cell proliferation in both temozolomide sensitive and insensitive GBM cell lines. In a human GBM xenograft model, a single daily dosage of MB does not activate AMPK signaling and no tumor regression was observed. In summary, the current study provides the first in vitro proof of concept that reversal of Warburg effect might be a novel therapy for GBM.
PMID: 23408428 [PubMed - as supplied by publisher] Free full text
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