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Desipramine induces apoptosis in rat glioma cells via endoplasmic reticulum stress-dependent CHOP pathway

  • Laboratory Investigation - Human/Animal Tissue
  • Published:
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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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Acknowledgment

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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Authors and Affiliations

  1. Department of Pharmacology, Institute of Medical Sciences, Shanghai Jiao Tong University School of Medicine, 280 South Chongqing Road, Shanghai, 200025, China

    Jian Ma, Yu Qiu, Lan Yang, Liang Peng, Zheng Xia, Li-Na Hou, Chao Fang, Hong Qi & Hong-Zhuan Chen

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  1. Jian Ma
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  2. Yu Qiu
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  3. Lan Yang
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Correspondence to Hong Qi or Hong-Zhuan Chen.

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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

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