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
Anti-Cancer Agents in Medicinal Chemistry
Title:Antidepressant Desipramine Leads to C6 Glioma Cell Autophagy: Implication for the Adjuvant Therapy of Cancer
Volume: 13 Issue: 2
Author(s): Jian Ma, Li-Na Hou, Zheng-Xing Rong, Peng Liang, Chao Fang, Hua-Fang Li, Hong Qi and Hong-Zhuan Chen
Affiliation:
Keywords: Desipramine, Adjuvant therapy, Autophagy, PERK, Endoplasmic reticulum stress
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.
Export Options
About this article
Cite this article as:
Ma Jian, Hou Li-Na, Rong Zheng-Xing, Liang Peng, Fang Chao, Li Hua-Fang, Qi Hong and Chen Hong-Zhuan, Antidepressant Desipramine Leads to C6 Glioma Cell Autophagy: Implication for the Adjuvant Therapy of Cancer, Anti-Cancer Agents in Medicinal Chemistry 2013; 13 (2) . https://dx.doi.org/10.2174/1871520611313020011
DOI https://dx.doi.org/10.2174/1871520611313020011 |
Print ISSN 1871-5206 |
Publisher Name Bentham Science Publisher |
Online ISSN 1875-5992 |
![](/images/wayfinder.jpg)
- Author Guidelines
- Bentham Author Support Services (BASS)
- Graphical Abstracts
- Fabricating and Stating False Information
- Research Misconduct
- Post Publication Discussions and Corrections
- Publishing Ethics and Rectitude
- Increase Visibility of Your Article
- Archiving Policies
- Peer Review Workflow
- Order Your Article Before Print
- Promote Your Article
- Manuscript Transfer Facility
- Editorial Policies
- Allegations from Whistleblowers
Related Articles
-
Conjugates of Cell Adhesion Peptides for Therapeutics and Diagnostics Against Cancer and Autoimmune Diseases
Current Topics in Medicinal Chemistry Role of Tyrosine Phosphatase Inhibitors in Cancer Treatment with Emphasis on SH2 Domain-Containing Tyrosine Phosphatases (SHPs)
Anti-Cancer Agents in Medicinal Chemistry Resisting the Resistance in Cancer: Cheminformatics Studies on Short- Path Base Excision Repair Pathway Antagonists Using Supervised Learning Approaches
Combinatorial Chemistry & High Throughput Screening Actions of the Anti-Angiogenic Compound Angiostatin in an Animal Model of Alzheimer’s Disease
Current Alzheimer Research miRNAs as Modulators of Cholesterol in Breast Cancer Stem Cells: An Approach to Overcome Drug Resistance in Cancer
Current Drug Targets Drug-Loaded Nanocarriers in Tumor Targeted Drug Delivery
Current Biotechnology Harnessing the Power of Cerenkov Luminescence Imaging for Gastroenterology: Cerenkov Luminescence Endoscopy
Current Medical Imaging Radiopharmaceuticals in Tumor Hypoxia Imaging: A Review Focused on Medicinal Chemistry Aspects
Anti-Cancer Agents in Medicinal Chemistry C-Glycosides and Aza-C-Glycosides as Potential Glycosidase and Glycosyltransferase Inhibitors
Current Topics in Medicinal Chemistry Molecular Link Mechanisms between Inflammation and Cancer
Current Pharmaceutical Design Synthesis and Evaluation of New Thiazolyl Hydrazone Derivatives as Potential Anticancer Agents
Letters in Drug Design & Discovery Targeting Histone Deacetylases in Neuroblastoma
Current Pharmaceutical Design Nutraceuticals and "Repurposed" Drugs of Phytochemical Origin in Prevention and Interception of Chronic Degenerative Diseases and Cancer
Current Medicinal Chemistry Role of Inflammatory Mediators in Angiogenesis
Current Drug Targets - Inflammation & Allergy MicroRNA-208a Potentiates Angiotensin II-triggered Cardiac Myoblasts Apoptosis via Inhibiting Nemo-like Kinase (NLK)
Current Pharmaceutical Design The Role of Blood-Brain Barrier Transporters in Pathophysiology and Pharmacotherapy of Stroke
Current Pharmaceutical Design Nanocarriers for Anticancer Drugs - New Trends in Nanomedicine
Current Drug Metabolism Exploration of (hetero)aryl Derived Thienylchalcones for Antiviral and Anticancer Activities
Medicinal Chemistry Working Hypothesis: Elimination of Cancer Stem Cells in Solid Tumors by Immuno-Gene Therapy Using Cancer Vaccines and Created-Inhibitory RNA
Current Cancer Therapy Reviews Targeting Calcium Channels to Block Tumor Vascularization
Recent Patents on Anti-Cancer Drug Discovery