Abstract |
Various antidepressants, mainly tricyclic antidepressants (TCAs) and selective serotonin reuptake inhibitors ( SSRIs), have exhibited potent anticancer properties in different cancer cell types. In the present study, desipramine (DMI), a representative of TCAs, was examined with respect to its apoptosis-inducing activity in rat C6 glioma cells and the underlying mechanism of action. DMI induced typical apoptotic morphology of chromatin condensation in rat glioma C6 cells and activated intracellular caspase 9 and caspase 3 with no change in mitochondrial membrane potential. Simultaneously, DMI significantly elevated expression of endoplasmic reticulum stress regulator CHOP/GADD153 and its targeting molecule GADD34. However, knockdown of CHOP by CHOP-specific short interfering RNA ( siRNA) could decrease the activity of intracellular caspase 3 and the cytotoxicity of DMI to C6 cells. These results revealed that the CHOP-dependent endoplasmic reticulum (ER) stress pathway is responsible for DMI-induced apoptosis in C6 cells.
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Authors | Jian Ma, Yu Qiu, Lan Yang, Liang Peng, Zheng Xia, Li-Na Hou, Chao Fang, Hong Qi, Hong-Zhuan Chen |
Journal | Journal of neuro-oncology
(J Neurooncol)
Vol. 101
Issue 1
Pg. 41-8
(Jan 2011)
ISSN: 1573-7373 [Electronic] United States |
PMID | 20549303
(Publication Type: Journal Article, Research Support, Non-U.S. Gov't)
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Chemical References |
- Antidepressive Agents, Tricyclic
- Ddit3 protein, rat
- RNA, Small Interfering
- Transcription Factor CHOP
- Desipramine
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Topics |
- Animals
- Antidepressive Agents, Tricyclic
(pharmacology)
- Apoptosis
(drug effects)
- Blotting, Western
- Cell Line, Tumor
- Desipramine
(pharmacology)
- Endoplasmic Reticulum
(drug effects, metabolism)
- Glioma
(metabolism)
- RNA, Small Interfering
- Rats
- Reverse Transcriptase Polymerase Chain Reaction
- Signal Transduction
(drug effects)
- Transcription Factor CHOP
(drug effects, metabolism)
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