title: The tricyclic antidepressant imipramine induces autophagic cell death in U-87MG glioma cells.
abstract: In this study, we investigated the antitumor effects of the tricyclic antidepressant 3-(10,11-dihydro-5H-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.
authors: Department of Biomedical Science and Technology, Research Center for Transcription Control, SMART Institute of Advanced Biomedical Science, Konkuk University, Seoul 143-701, Republic of Korea.
authors: Seung-Hyun
authors: SH
authors: Jeon
authors: Se Hyun
authors: SH
authors: Kim
authors: Yeni
authors: Y
authors: Kim
authors: Yong Sik
authors: YS
authors: Kim
authors: Yoongho
authors: Y
authors: Lim
authors: Young Han
authors: YH
authors: Lee
authors: Soon Young
authors: SY
authors: Shin
mesh_terms: D000818:Animals; D000929:Antidepressive Agents, Tricyclic / Q000494:pharmacology*; D000970:Antineoplastic Agents / Q000494:pharmacology*; D051017:Apoptosis Regulatory Proteins / Q000235:genetics; D001343:Autophagy / Q000187:drug effects* / Q000235:genetics; D000071186:Beclin-1; D045744:Cell Line, Tumor; D055785:Gene Knockdown Techniques; D005909:Glioblastoma / Q000201:enzymology*; D006801:Humans; D007099:Imipramine / Q000494:pharmacology*; D008565:Membrane Proteins / Q000235:genetics; D008869:Microtubule-Associated Proteins / Q000378:metabolism; D051059:PTEN Phosphohydrolase / Q000235:genetics; D000081082:Phosphoinositide-3 Kinase Inhibitors; D051057:Proto-Oncogene Proteins c-akt / Q000037:antagonists & inhibitors; D051381:Rats; D058570:TOR Serine-Threonine Kinases / Q000037:antagonists & inhibitors
chemical_list: D000929:Antidepressive Agents, Tricyclic; D000970:Antineoplastic Agents; D051017:Apoptosis Regulatory Proteins; C491997:BECN1 protein, human; D000071186:Beclin-1; C477012:MAP1LC3A protein, human; D008565:Membrane Proteins; D008869:Microtubule-Associated Proteins; D000081082:Phosphoinositide-3 Kinase Inhibitors; D051057:Proto-Oncogene Proteins c-akt; D058570:TOR Serine-Threonine Kinases; D051059:PTEN Phosphohydrolase; D007099:Imipramine