2009 Fiscal Year Final Research Report
Overcoming therapy resistance of glioma cells via modulation of mitochondrial energy metabolism
| Project/Area Number |
20791002
|
|---|
| Research Category |
Grant-in-Aid for Young Scientists (B)
|
| Allocation Type | Single-year Grants |
|---|
| Research Field |
Cerebral neurosurgery
|
|---|
| Research Institution | Yamagata University |
|---|
Principal Investigator |
TOMIYAMA Arata Yamagata University, 医学部, 助教 (40385810)
|
|---|
| Project Period (FY) |
2008 – 2009
|
| Keywords | グリオーマ / エネルギー代謝 |
|---|
| Research Abstract |
Cancer cells are prone to carry out anaerobic glycolysis even in the presence of ample oxygen. This unique property of cancer cells is widely known as "Warburg effect", but why cancer cells choose to carry out such an energetically-inefficient, anaerobic metabolism in the place of oxidative metabolism, which is far more efficient in terms of ATP production, has remained a big enigma for decades in the field of cancer research. As a possible explanation, we have recently shown that oxidative phosphorylation, but not anaerobic glycolysis, is required for the activation of Bax and Bak, an essential step in the process of mitochondria-mediated apoptosis. Thus, Warburg effect could be a crafty strategy of cancer cells to evade apoptosis at the expense of energy production efficiency. Conversely, our findings also suggested the possibility that reversal of Warburg effect could render cancer cells susceptible to mitochondria-mediated apoptosis and hence to anti-cancer therapies. In this project, therefore, we searched for natural and chemical compounds that recover/promote oxidative metabolism in glioma cells and thereby render the cells sensitive to temozolomide, the first-choice chemotherapeutic agent in the management of malignant gliomas. Here we report that we have successfully identified a natural compound having such activities.
|
