Abstract
In this study, we investigated the antitumor effects of the tricyclic antidepressant 3-(10,11-dihydro-5. H-dibenzo[. b,. f]azepin-5-yl)- N,. N-dimethylpropan-1-amine (imipramine) on glioma cells. We found that exposure of U-87MG cells to imipramine resulted in the inhibition of PI3K/Akt/mTOR signaling, reduction of clonogenicity, and induction of cell death. Imipramine stimulated the formation of acidic vesicular organelles, the conversion of LC3-I to LC3-II, and the redistribution of LC3 to autophagosomes, suggesting that it stimulates the progression of autophagy. It did not, however, induce apoptosis. We further showed that knockdown of Beclin-1 using siRNA abrogated imipramine-induced cell death. These results suggest that imipramine exerts antitumor effects on PTEN-null U-87MG human glioma cells by inhibiting PI3K/Akt/mTOR signaling and by inducing autophagic cell death.
Original language | English |
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Pages (from-to) | 311-317 |
Number of pages | 7 |
Journal | Biochemical and Biophysical Research Communications |
Volume | 413 |
Issue number | 2 |
DOIs | |
State | Published - 23 Sep 2011 |
Keywords
- Autophagy
- Glioma
- Imipramine
- MTOR
- Type II programmed cell death