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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We gratefully thank National Natural Science Foundation of China (no. 30672442, no. 30600788, and no. 30873179) and National Basic Research Program of China (no. 2010CB529806) for financial support.
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Ma, J., Qiu, Y., Yang, L. et al. Desipramine induces apoptosis in rat glioma cells via endoplasmic reticulum stress-dependent CHOP pathway. J Neurooncol 101, 41–48 (2011). https://doi.org/10.1007/s11060-010-0237-2
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DOI: https://doi.org/10.1007/s11060-010-0237-2