Antidepressant Desipramine Leads to C6 Glioma Cell Autophagy: Implication for the Adjuvant Therapy of Cancer

ISSN: 1875-5992 (Online)
ISSN: 1871-5206 (Print)


Volume 16, 12 Issues, 2016


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Anti-Cancer Agents in Medicinal Chemistry

Formerly: Current Medicinal Chemistry - Anti-Cancer Agents

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Michelle Prudhomme
Universite Blaise Pascal - C.N.R.S
Aubiere Cedex
France


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Antidepressant Desipramine Leads to C6 Glioma Cell Autophagy: Implication for the Adjuvant Therapy of Cancer



Anti-Cancer Agents in Medicinal Chemistry, 13(2): 254-260.

Author(s): Jian Ma, Li-Na Hou, Zheng-Xing Rong, Peng Liang, Chao Fang, Hua-Fang Li, Hong Qi and Hong-Zhuan Chen.

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

Abstract

Depression is the most common psychiatric syndrome in cancer patients and adversely affects anti-cancer immune system and life quality of patients. Antidepressant desipramine (DMI) is clinically prescribed in the auxiliary treatment of cancer patients. Increasing evidences suggest that DMI has a broad spectrum of target-off biological effects, such as anticancer properties. Our previous study revealed that DMI at the clinical relevant concentrations could induce CHOP-dependent apoptotic death in C6 glioma cells. In this study, we further explored the pro-autophagic effect of DMI in C6 glioma cells and its underlying mechanism. Treatment with DMI could induce autophagic cell death characterized by the formation of autophagosome and the elevated level of autophagic protein Beclin-1 and cellular redistribution of marker LC3. Meanwhile, DMI inhibited the activation of PI3K-AKT-mTOR pathway which is considered as a negative regulator of autophagy. Furthermore, DMI activated PERK-eIF2α and ATF6 of endoplasmic reticulum (ER) stress pathway, while knockdown of PERK with the PERK-specific short interfering RNA (siRNA) could obviously attenuate the autophagy. The results strongly suggested that DMI could induce autophagy through the PERK-ER stress pathway in C6 glioma cells. Our findings provided new insights into another beneficial potential of antidepressant DMI in the adjuvant therapy of cancer.

Keywords:

Desipramine, Adjuvant therapy, Autophagy, PERK, Endoplasmic reticulum stress .



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Article Details

Volume: 13
Issue Number: 2
First Page: 254
Last Page: 260
Page Count: 7
DOI: 10.2174/1871520611313020011
Price: $58
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