The tricyclic antidepressant imipramine induces autophagic cell death in U-87MG glioma cells

Seung Hyun Jeon, Se Hyun Kim, Yeni Kim, Yong Sik Kim, Yoongho Lim, Young Han Lee, Soon Young Shin

Research output: Contribution to journalArticle

52 Citations (Scopus)

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 languageEnglish
Pages (from-to)311-317
Number of pages7
JournalBiochemical and Biophysical Research Communications
Volume413
Issue number2
DOIs
StatePublished - 23 Sep 2011

Fingerprint

Imipramine
Tricyclic Antidepressive Agents
Autophagy
Cell death
Glioma
Phosphatidylinositol 3-Kinases
Cell Death
Organelles
Small Interfering RNA
Amines
Apoptosis

Keywords

  • Autophagy
  • Glioma
  • Imipramine
  • MTOR
  • Type II programmed cell death

Cite this

Jeon, Seung Hyun ; Kim, Se Hyun ; Kim, Yeni ; Kim, Yong Sik ; Lim, Yoongho ; Lee, Young Han ; Shin, Soon Young. / The tricyclic antidepressant imipramine induces autophagic cell death in U-87MG glioma cells. In: Biochemical and Biophysical Research Communications. 2011 ; Vol. 413, No. 2. pp. 311-317.
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The tricyclic antidepressant imipramine induces autophagic cell death in U-87MG glioma cells. / Jeon, Seung Hyun; Kim, Se Hyun; Kim, Yeni; Kim, Yong Sik; Lim, Yoongho; Lee, Young Han; Shin, Soon Young.

In: Biochemical and Biophysical Research Communications, Vol. 413, No. 2, 23.09.2011, p. 311-317.

Research output: Contribution to journalArticle

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