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 |
Call for Papers in Thematic Issues
Induction of cell death in cancer cells by modulating telomerase activity using small molecule drugs
Telomeres are distinctive but short stretches present at the corners of chromosomes and aid in stabilizing chromosomal makeup. Resynthesis of telomeres supported by the activity of reverse transcriptase ribonucleoprotein complex telomerase. There is no any telomerase activity in human somatic cells, but the stem cells and germ cells undergone telomerase ...read more
Role of natural compounds as anti anti-cancer agents
Cancer is considered the leading cause of worldwide mortality, accounting for nearly 10 million deaths in 2022. Cancer outcome can be improved through an appropriate screening and early detection and through an efficient clinical treatment. Chemotherapy remains an important approach in treatment o f several types of cancers, even though ...read more
Signaling and enzymatic modulators in cancer treatment
Cancer accounts for nearly 10 million deaths in 2022 and is considered the leading cause of worldwide mortality. Cancer outcome can be improved through an appropriate screening and early detection and through an efficient clinical treatment. Chemotherapy, radiotherapy and surgery are the most important approach for the treatment of several ...read more
- Author Guidelines
- 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
-
Rational Drug Development Using Gene-Targeted Agents and Their Application in Anti-Gene Radiotherapy
Current Genomics Molecular Markers of Angiogenesis and Metastasis in Lines of Oral Carcinoma after Treatment with Melatonin
Anti-Cancer Agents in Medicinal Chemistry Targeting Cancer Stem Cells with Natural Products
Current Drug Targets Insight to Physiology and Pathology of Zinc(II) Ions and Their Actions in Breast and Prostate Carcinoma
Current Medicinal Chemistry Membrane Domains and the “Lipid Raft” Concept
Current Medicinal Chemistry How to Inhibit Telomerase Activity for Cancer Therapy
Current Medicinal Chemistry - Anti-Cancer Agents RNA Interference in Cancer: Targeting the Anti-Apoptotic Protein c-FLIP for Drug Discovery
Mini-Reviews in Medicinal Chemistry Peptides as Tight Junction Modulators
Current Pharmaceutical Design Target Therapies in Pancreatic Carcinoma
Current Medicinal Chemistry α-Synuclein Misfolding and Neurodegenerative Diseases
Current Protein & Peptide Science A Combination of Two Antioxidants (An SOD Mimic and Ascorbate) Produces a Pro-Oxidative Effect Forcing Escherichia coli to Adapt Via Induction of oxyR Regulon
Anti-Cancer Agents in Medicinal Chemistry Adaptor Protein 3BP2 and Cherubism
Current Medicinal Chemistry Bortezomib in the Treatment of Cancer
Recent Patents on Anti-Cancer Drug Discovery Factors Interacting with HIF-1α mRNA: Novel Therapeutic Targets
Current Pharmaceutical Design One-Step Synthesis of 1H-1,2,3-Triazol-1-Ylmethyl-2,3-Dihydronaphtho[1,2-b]furan- 4,5-Diones
Current Organic Synthesis Protein Kinase C and Prostate Carcinogenesis: Targeting the Cell Cycle and Apoptotic Mechanisms
Current Drug Targets Unsupervised End-to-End Brain Tumor Magnetic Resonance Image Registration Using RBCNN: Rigid Transformation, B-Spline Transformation and Convolutional Neural Network
Current Medical Imaging Surface Markers of Cancer Stem Cells in Solid Tumors
Current Stem Cell Research & Therapy Gene Therapy Targeting Nuclear Factor-κB: Towards Clinical Application in Inflammatory Diseases and Cancer
Current Gene Therapy Bioprocessing of Baculovirus Vectors: A Review
Current Gene Therapy