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Research Paper
Decreased Glycolytic Metabolism Accelerates Apoptosis in Response to 2-Acetyl Furanonaphthoquinone in K1735 Melanoma Irrespective of bcl-2 Overexpression
Leobaldo Solórzano, Mary Strasberg Rieber, Jose D. Medina and Manuel Rieber
volume 4 | issue 3
march 2005Pages: 329-335
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Solid tumors are often placed under stress conditions, such as glucose starvation which may result in topoisomerase II drug resistance. In this study , we investigated whether glucose deprivation or substitution by fructose regulates tumor cell apoptosis induced by 2-acetyl furanonaphthoquinone (FNQ) . We now show that FNQ exerts much greater antitumor activity than either 7-methoxy 2-ethyl FNQ or 2-ethyl FNQ. Whereas 0.8 µM FNQ induces apoptosis after 16 hours in glucose-supplemented conditions irrespective of bcl-2 overexpression in K1735 melanoma , 0.5 µM FNQ is also effective within 12 hours in low glucose or in fructose-supplemented medium Under the latter conditions, apoptosis-associated PARP cleavage and cytosolic cytochrome C are increased, together with induction and partial translocation to mitochondria of phosphorylated Jun-N-terminal kinase and massive upregulation of mitochondrial Mn superoxide dismutase. We propose that mitochondrial co-localization of these activities is important in this synergistic anti-tumor effect of FNQ and glucose depletion . Since glucose limitation slows proliferation and decreases efficacy of some genotoxic drugs that trigger apoptosis in rapidly dividing cells, we propose evaluating FNQ as a novel therapeutic anti-cancer adjuvant against slowly proliferating tumors .
We now provide open access to journal articles published online for one year or more. This article may be downloaded at the following link:
Download PDFIf the document does not open, please right-click on the link (control-click on a Macintosh) and select the option to save the file to disk.