title: Desipramine induces apoptosis in rat glioma cells via endoplasmic reticulum stress-dependent CHOP pathway.
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.
authors.affiliation: Department of Pharmacology, Institute of Medical Sciences, Shanghai Jiao Tong University School of Medicine, Shanghai, 200025, China.
authors.forename: Jian
authors.initials: J
authors.lastname: Ma
authors.forename: Yu
authors.initials: Y
authors.lastname: Qiu
authors.forename: Lan
authors.initials: L
authors.lastname: Yang
authors.forename: Liang
authors.initials: L
authors.lastname: Peng
authors.forename: Zheng
authors.initials: Z
authors.lastname: Xia
authors.forename: Li-Na
authors.initials: LN
authors.lastname: Hou
authors.forename: Chao
authors.initials: C
authors.lastname: Fang
authors.forename: Hong
authors.initials: H
authors.lastname: Qi
authors.forename: Hong-Zhuan
authors.initials: HZ
authors.lastname: Chen
mesh_terms: D000818:Animals; D000929:Antidepressive Agents, Tricyclic / Q000494:pharmacology*; D017209:Apoptosis / Q000187:drug effects*; D015153:Blotting, Western; D045744:Cell Line, Tumor; D003891:Desipramine / Q000494:pharmacology*; D004721:Endoplasmic Reticulum / Q000187:drug effects / Q000378:metabolism; D005910:Glioma / Q000378:metabolism*; D034741:RNA, Small Interfering; D051381:Rats; D020133:Reverse Transcriptase Polymerase Chain Reaction; D015398:Signal Transduction / Q000187:drug effects*; D051742:Transcription Factor CHOP / Q000187:drug effects* / Q000378:metabolism
chemical_list: D000929:Antidepressive Agents, Tricyclic; C497251:Ddit3 protein, rat; D034741:RNA, Small Interfering; D051742:Transcription Factor CHOP; D003891:Desipramine