Abstract
We have shown previously that withaferin A (WA), which is a highly promising anticancer constituent of Ayurvedic medicine plant Withania somnifera, inhibits viability of cultured breast cancer cells in association with reactive oxygen species (ROS)-dependent apoptosis induction. Because ROS production is implicated in induction of autophagy, which is an evolutionary conserved process for bulk degradation of cellular components including organelles (e.g., mitochondria) and considered a valid cancer chemotherapeutic target, we questioned whether WA treatment resulted in autophagy induction. Indeed exposure of MDA-MB-231 and MCF-7 human breast cancer cells as well as a spontaneously immortalized and non-tumorigenic normal human mammary epithelial cell line (MCF-10A) to pharmacologic concentration of WA resulted in autophagy as evidenced by transmission electron microscopy, processing of microtubuleassociated protein 1 light chain 3 isoform B, and/or acridine orange staining. Inhibition of MDA-MB-231 xenograft growth in vivo by WA administration was also associated with a significant increase in level of LC3 protein in the tumor. However, WA-mediated inhibition of MDA-MB-231 and MCF-7 cell viability was not compromised either by pharmacological suppression of autophagy using 3-methyl adenine or genetic repression of autophagy by RNA interference of Atg5, a critical component of the autophagic machinery. Finally, Beclin1 was dispensable for WA-mediated autophagy as well as inhibition of MDA-MB-231 cell viability. Based on these observations we conclude that autophagy induction fails to have any meaningful impact on WA-mediated lethality in breast cancer cells, which may be a therapeutic advantage because autophagy serves to protect against apoptosis by several anticancer agents.
Keywords: Autophagy, Atg5, Beclin1, breast cancer, MCF-7, MDA-MB-231, withaferin A.
Current Cancer Drug Targets
Title:Autophagy Fails to Alter Withaferin A-Mediated Lethality in Human Breast Cancer Cells
Volume: 13 Issue: 6
Author(s): Eun-Ryeong Hahm and Shivendra V. Singh
Affiliation:
Keywords: Autophagy, Atg5, Beclin1, breast cancer, MCF-7, MDA-MB-231, withaferin A.
Abstract: We have shown previously that withaferin A (WA), which is a highly promising anticancer constituent of Ayurvedic medicine plant Withania somnifera, inhibits viability of cultured breast cancer cells in association with reactive oxygen species (ROS)-dependent apoptosis induction. Because ROS production is implicated in induction of autophagy, which is an evolutionary conserved process for bulk degradation of cellular components including organelles (e.g., mitochondria) and considered a valid cancer chemotherapeutic target, we questioned whether WA treatment resulted in autophagy induction. Indeed exposure of MDA-MB-231 and MCF-7 human breast cancer cells as well as a spontaneously immortalized and non-tumorigenic normal human mammary epithelial cell line (MCF-10A) to pharmacologic concentration of WA resulted in autophagy as evidenced by transmission electron microscopy, processing of microtubuleassociated protein 1 light chain 3 isoform B, and/or acridine orange staining. Inhibition of MDA-MB-231 xenograft growth in vivo by WA administration was also associated with a significant increase in level of LC3 protein in the tumor. However, WA-mediated inhibition of MDA-MB-231 and MCF-7 cell viability was not compromised either by pharmacological suppression of autophagy using 3-methyl adenine or genetic repression of autophagy by RNA interference of Atg5, a critical component of the autophagic machinery. Finally, Beclin1 was dispensable for WA-mediated autophagy as well as inhibition of MDA-MB-231 cell viability. Based on these observations we conclude that autophagy induction fails to have any meaningful impact on WA-mediated lethality in breast cancer cells, which may be a therapeutic advantage because autophagy serves to protect against apoptosis by several anticancer agents.
Export Options
About this article
Cite this article as:
Hahm Eun-Ryeong and Singh V. Shivendra, Autophagy Fails to Alter Withaferin A-Mediated Lethality in Human Breast Cancer Cells, Current Cancer Drug Targets 2013; 13 (6) . https://dx.doi.org/10.2174/15680096113139990039
DOI https://dx.doi.org/10.2174/15680096113139990039 |
Print ISSN 1568-0096 |
Publisher Name Bentham Science Publisher |
Online ISSN 1873-5576 |
Call for Papers in Thematic Issues
Advances in Cancer Biomarkers and Potential Drug Targets: From Diagnosis to Therapy
Cancer biomarkers play a crucial role in the diagnosis, prognosis, and treatment of cancer. They provide valuable information for cancer detection, risk assessment, treatment selection, and monitoring response to therapy. With advancements in molecular biology and high-throughput technologies, there has been an increasing interest in identifying and characterizing cancer biomarkers ...read more
Novel Therapeutic Approaches to Target Drug Resistant Tumors
With the development of disciplines such as chemical biology and molecular biology, the genes or proteins closely related to tumor occurrence and development have gradually become clear. Targeted therapies targeting these genes or proteins provide more effective methods for tumor treatment. Tumor targeted drugs generally only act on specific targets ...read more
ROLE OF IMMUNE AND GENOTOXIC RESPONSE BIOMARKERS IN TUMOR MICROENVIRONMENT IN CANCER DIAGNOSIS AND TREATMENT
Biological biomarkers have been used in medical research as an indicator of a normal or abnormal process inside the body, or of a disease. Nowadays, various researchers are in process to explore and investigate the biological markers for the early assessment of cancer. DNA Damage response (DDR) pathways and immune ...read more
Targeting the battlefield between host and tumor: basic research and clinical practice on reshaping tumor immune microenvironment
Immune system protects host against malignant tumors through effector cells and molecules. Cancer development and its response to therapy are regulated by inflammation, which either promotes or suppresses cancer progression. Chronic inflammation facilitates cancer progression and treatment resistance, whereas induction of acute inflammatory reactions often lead to anti-cancer immune responses. ...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
-
Transport of Bupropion and its Metabolites by the Model CHO and HEK293 Cell Lines
Drug Metabolism Letters The Effects of 1,3,5-trisubstituted Indole Derivatives on Cell Growth, Apoptosis and MMP-2/9 mRNA Expression of MCF-7 Human Breast Cancer Cells
Anti-Cancer Agents in Medicinal Chemistry Current Management of Alcoholic Liver Disease
Current Drug Abuse Reviews MiRNAs in Human Cancers: The Diagnostic and Therapeutic Implications
Current Pharmaceutical Design Overview of SLC22A and SLCO Families of Drug Uptake Transporters in the Context of Cancer Treatments
Current Drug Metabolism Electron Emission of Phytohormone Genistein. Pathway for Communication
Current Bioactive Compounds Recent Research Trends on Bismuth Compounds in Cancer Chemoand Radiotherapy
Current Medicinal Chemistry Tumor-Derived Exosomes Contain microRNAs with Immunological Function: Implications for a Novel Immunosuppression Mechanism
MicroRNA Gold Nanoparticles: Promising Agent to Improve the Diagnosis and Therapy of Cancer
Current Drug Metabolism Regulation of Runx2 and Its Signaling Pathways by MicroRNAs in Breast Cancer Metastasis
Current Protein & Peptide Science PPARs in Diseases: Control Mechanisms of Inflammation
Current Medicinal Chemistry Mitoxantrone Targets the ATP-binding Site of FAK, Binds the FAK Kinase Domain and Decreases FAK, Pyk-2, c-Src, and IGF-1R In Vitro Kinase Activities
Anti-Cancer Agents in Medicinal Chemistry Immunotherapy in Breast Cancer- Paving New Roads?
Current Molecular Pharmacology Redox Homeostasis, Bioactive Agents and Transduction Therapy
Current Signal Transduction Therapy Histone Deacetylase Inhibitors: An Attractive Strategy for Cancer Therapy
Current Medicinal Chemistry Detection of Predictive Markers for Therapeutic Stratification of Salivary Glands Tumors
Current Drug Targets Significance of 1,3,4-Oxadiazole Containing Compounds in New Drug Development
Current Drug Research Reviews Nano-Phytosome: A Developing Platform for Herbal Anti-Cancer Agents in Cancer Therapy
Current Drug Targets Basic Mechanisms Involved in the Anti-Cancer Effects of Melatonin
Current Medicinal Chemistry The Cytoskeleton as a Therapeutic Target in Childhood Acute Leukemia:Obstacles and Opportunities
Current Drug Targets