Targeting glucose consumption and autophagy in myeloma with the novel nucleoside analogue 8-aminoadenosine.
Mala Shanmugam, Samuel K McBrayer, Jun Qian, Kiril Raikoff, Michael J Avram, Seema Singhal, Varsha Gandhi, Paul T Schumacker, Nancy L Krett, Steven T Rosen
文献索引:J. Biol. Chem. 284(39) , 26816-30, (2009)
全文:HTML全文
摘要
Multiple myeloma, an incurable plasma cell malignancy, is characterized by altered cellular metabolism and resistance to apoptosis. Recent connections between glucose metabolism and resistance to apoptosis provide a compelling rationale for targeting metabolic changes in cancer. In this study, we have examined the ability of the purine analogue 8-aminoadenosine to acutely reduce glucose consumption by regulating localization and expression of key glucose transporters. Myeloma cells counteracted the metabolic stress by activating autophagy. Co-treatment with inhibitors of autophagy results in marked enhancement of cell death. Glucose consumption by drug-resistant myeloma cells was unaffected by 8-aminoadenosine, and accordingly, no activation of autophagy was observed. However, these cells can be sensitized to 8-aminoadenosine under glucose-limiting conditions. The prosurvival autophagic response of myeloma to nutrient deprivation or to nucleoside analogue treatment has not been described previously. This study establishes the potential of metabolic targeting as a broader means to kill and sensitize myeloma and identifies a compound that can achieve this goal.
相关化合物
相关文献:
2007-01-01
[Nucleic Acids Symp. Ser. (51) , 17-8, (2007)]
2005-04-01
[Mol. Cancer Ther. 4(4) , 569-77, (2005)]
2004-11-01
[Mol. Cancer Ther. 3(11) , 1411-20, (2004)]
2005-09-15
[Clin. Cancer Res. 11(18) , 6745-52, (2005)]
2010-01-01
[Mol. Cancer Ther. 9(1) , 236-45, (2010)]