![[Feedback]](/icons/banner/feedbackACT.gif){kind=icon}
![[For Subscribers]](/icons/banner/subscriberACT.gif){kind=icon}
![[Archive]](/icons/banner/archiveACT.gif){kind=icon}
![[Search]](/icons/banner/searchACT.gif){kind=icon}
|
|
|
|
|
||
| |||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
Received for publication December 4, 2006.
Revised March 26, 2007.
Accepted for publication March 28, 2007.
Autophagy is a response of cancer cells to various anticancer therapies. It is designated as programmed cell death type II and characterized by formation of autophagic vacuoles in the cytoplasm. The Akt/mammalian target of rapamycin (mTOR)/p70S6K and the extracellular signal-regulated kinases 1/2 (ERK1/2) pathways are two major pathways which regulate autophagy induced by nutrient starvation. These pathways are also frequently associated with oncogenesis in a variety of cancer cell types, including malignant gliomas. However, few studies have examined both of these signal pathways in the context of anticancer therapy-induced autophagy in cancer cells, and autophagy's effect on cell death remains unclear. Here, we examined the anticancer efficacy and mechanisms of curcumin, a natural compound with low toxicity in normal cells, in U87-MG and U373-MG malignant glioma cells. Curcumin induced G2/M arrest and non-apoptotic autophagic cell death in both cell types. It inhibited the Akt/mTOR/p70S6K pathway and activated the ERK1/2 pathway, resulting in induction of autophagy. Interestingly, activation of the Akt pathway inhibited curcumin-induced autophagy and cytotoxicity, whereas inhibition of the ERK1/2 pathway inhibited curcumin-induced autophagy and induced apoptosis, thus resulting in enhanced cytotoxicity. These results imply that the effect of autophagy on cell death may be pathway specific. In the subcutaneous xenograft model of U87-MG cells, curcumin inhibited tumor growth significantly (P < 0.05) and induced autophagy. These results suggest that curcumin has high anticancer efficacy in vitro and in vivo by inducing autophagy and warrant further investigation toward possible clinical application in patients with malignant glioma.
Key words:
MAP Kinase, NFkappaB, Regulation - physiological
This article has been cited by other articles:
|
|
 |
|
  L. A. Lambert, N. Qiao, K. K. Hunt, D. H. Lambert, G. B. Mills, L. Meijer, and K. Keyomarsi Autophagy: A Novel Mechanism of Synergistic Cytotoxicity between Doxorubicin and Roscovitine in a Sarcoma Model Cancer Res., October 1, 2008; 68(19): 7966 - 7974. [Abstract] [Full Text] [PDF]
|
|
|
|
 |
|
 D. Wang, M. S. Veena, K. Stevenson, C. Tang, B. Ho, J. D. Suh, V. M. Duarte, K. F. Faull, K. Mehta, E. S. Srivatsan, et al. Liposome-Encapsulated Curcumin Suppresses Growth of Head and Neck Squamous Cell Carcinoma In vitro and in Xenografts through the Inhibition of Nuclear Factor {kappa}B by an AKT-Independent Pathway Clin. Cancer Res., October 1, 2008; 14(19): 6228 - 6236. [Abstract] [Full Text] [PDF]
|
|
|
|
 |
|
 S. Yu, G. Shen, T. O. Khor, J.-H. Kim, and A.-N. T. Kong Curcumin inhibits Akt/mammalian target of rapamycin signaling through protein phosphatase-dependent mechanism Mol. Cancer Ther., September 1, 2008; 7(9): 2609 - 2620. [Abstract] [Full Text] [PDF]
|
|
|
|
 |
|
 K. Singletary and J. Milner Diet, Autophagy, and Cancer: A Review Cancer Epidemiol. Biomarkers Prev., July 1, 2008; 17(7): 1596 - 1610. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
Z. Yan, H. Zou, F. Tian, J. R. Grandis, A. J. Mixson, P. Y. Lu, and L.-Y. Li Human rhomboid family-1 gene silencing causes apoptosis or autophagy to epithelial cancer cells and inhibits xenograft tumor growth Mol. Cancer Ther., June 1, 2008; 7(6): 1355 - 1364. [Abstract] [Full Text] [PDF]
|
|
|
|
 |
|
 S. J. Kim, T. G. Son, H. R. Park, M. Park, M.-S. Kim, H. S. Kim, H. Y. Chung, M. P. Mattson, and J. Lee Curcumin Stimulates Proliferation of Embryonic Neural Progenitor Cells and Neurogenesis in the Adult Hippocampus J. Biol. Chem., May 23, 2008; 283(21): 14497 - 14505. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
A. B. Kunnumakkara, P. Diagaradjane, S. Guha, A. Deorukhkar, S. Shentu, B. B. Aggarwal, and S. Krishnan Curcumin Sensitizes Human Colorectal Cancer Xenografts in Nude Mice to {gamma}-Radiation by Targeting Nuclear Factor-{kappa}B-Regulated Gene Products Clin. Cancer Res., April 1, 2008; 14(7): 2128 - 2136. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
B. H. Choi, C. G. Kim, Y.-S. Bae, Y. Lim, Y. H. Lee, and S. Y. Shin p21Waf1/Cip1 Expression by Curcumin in U-87MG Human Glioma Cells: Role of Early Growth Response-1 Expression Cancer Res., March 1, 2008; 68(5): 1369 - 1377. [Abstract] [Full Text] [PDF]
|
|
|
|
 |
|
 R. A. Newman, Y. Kondo, T. Yokoyama, S. Dixon, C. Cartwright, D. Chan, M. Johansen, and Peiying Yang Autophagic Cell Death of Human Pancreatic Tumor Cells Mediated by Oleandrin, a Lipid-Soluble Cardiac Glycoside Integr Cancer Ther, December 1, 2007; 6(4): 354 - 364. [Abstract] [PDF]
|
|
 |
 |
 |
|
 |
 |
 |
