Back to Search
Start Over
Curcumin inhibits urothelial tumor development by suppressing IGF2 and IGF2-mediated PI3K/AKT/mTOR signaling pathway.
- Source :
-
Journal of Drug Targeting . Aug2017, Vol. 25 Issue 7, p626-636. 11p. - Publication Year :
- 2017
-
Abstract
- We have previously reported that curcumin inhibits urothelial tumor development in a rat bladder carcinogenesis model. In this study, we report that curcumin inhibits urothelial tumor development by suppressing IGF2 and IGF2-mediated PI3K/AKT/mTOR signaling pathway. Curcumin inhibits IGF2 expression at the transcriptional level and decreases the phosphorylation levels of IGF1R and IRS-1 in bladder cancer cells andN-methyl-N-nitrosourea (MNU)-induced urothelial tumor tissue. Ectopic expression of IGF2 and IGF1R, but not IGF1, in bladder cancer cells restored this process, suggesting that IGF2 is a target of curcumin. Moreover, introduction of constitutively active AKT1 abolished the inhibitory effect of curcumin on cell proliferation, migration, and restored the phosphorylation levels of 4E-BP1 and S6K1, suggesting that curcumin functions via suppressing IGF2-mediated AKT/mTOR signaling pathway. In summary, our results reveal that suppressing IGF2 and IGF2-mediated PI3K/AKT/mTOR signaling pathway is one of the mechanisms of action of curcumin. Our findings suggest a new therapeutic strategy against human bladder cancer caused by aberrant activation of IGF2, which are useful for translational application of curcumin. [ABSTRACT FROM AUTHOR]
Details
- Language :
- English
- ISSN :
- 1061186X
- Volume :
- 25
- Issue :
- 7
- Database :
- Academic Search Index
- Journal :
- Journal of Drug Targeting
- Publication Type :
- Academic Journal
- Accession number :
- 123351966
- Full Text :
- https://doi.org/10.1080/1061186X.2017.1306535