Details

Autor(en) / Beteiligte

• Poteet, Ethan
• Choudhury, Gourav Roy
• Winters, Ali
• Li, Wenjun
• Ryou, Myoung-Gwi
• Liu, Ran
• Tang, Lin
• Ghorpade, Anuja
• Wen, Yi
• Yuan, Fang
• Keir, Stephen T.
• Yan, Hai
• Bigner, Darell D.
• Simpkins, James W.
• Yang, Shao-Hua

Titel

Reversing the Warburg Effect as a Treatment for Glioblastoma

Ist Teil von

• The Journal of biological chemistry, 2013-03, Vol.288 (13), p.9153-9164

Ort / Verlag

United States: Elsevier Inc

Erscheinungsjahr

2013

Link zum Volltext

Quelle

MEDLINE

Beschreibungen/Notizen

• 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, 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 AMP-activated protein kinase 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. Background: Glioblastoma is the most prevalent brain tumor with the poorest prognosis. Results: Methylene blue enhances oxygen consumption, reduces lactate production, and inhibits glioblastoma cell proliferation. Conclusion: Reversal of the Warburg effect could inhibit glioblastoma cell proliferation. Significance: Modulation of cancer cell bioenergetics and reversal of Warburg effect might provide a novel therapy for glioblastoma.