Abstract
Background: It has been reported that diallyl disulfide (DADS) has anti-proliferative activity in many cancers.
Objective: The purpose of this study was to investigate the functions of DADS and the underlying mechanisms of its effect in breast cancer stem cells (BCSCs).
Method: Mammosphere formation assay, glucose consumption assay, lactate production assay and mouse xenograft experiments were performed to explore the functions of DADS in BCSCs. ATPase activity assay, western blotting and immunohistochemistry (IHC) assay were conduct to explore the mechanisms underlying the effects of DADS in BCSCs.
Results: The results showed that DADS suppressed cell stemness and glucose metabolism in BCSCs. In vivo mouse xenograft experiments showed that DADS inhibited the proliferation and metastasis of BCSCs. Then, we continued to explore the mechanisms underlying the effects of DADS in BCSCs and found that DADS acts by targeting CD44, Pyruvate kinase M2 (PKM2) and AMP-activated protein kinase (AMPK) signaling pathways. IHC analysis of 125 breast cancer patients’ tissues demonstrated that CD44, PKM2 and AMPK expression levels were positively correlated. In addition, positive CD44, PKM2 and AMPK expression was associated with poor patient overall survival (OS) and disease-free survival (DFS).
Conclusion: In summary, DADS suppresses cell stemness, proliferation, metastasis and glucose metabolism in BCSCs partly through the inhibition of CD44/PKM2/AMPK. DADS may be used as a potential therapy for breast cancer treatment.
Keywords: Diallyl disulfide, breast cancer stem cell, CD44, PKM2, AMPK, xenograft.
Current Cancer Drug Targets
Title:Diallyl Disulfide Inhibits Breast Cancer Stem Cell Progression and Glucose Metabolism by Targeting CD44/PKM2/AMPK Signaling
Volume: 18 Issue: 6
Author(s): Xinhua Xie, Xiaojia Huang, Hailin Tang, Feng Ye, Lu Yang, Xiaofang Guo, Zhi Tian, Xiaofang Xie, Cheng Peng* Xiaoming Xie*
Affiliation:
- School of Pharmacy, Chengdu University of Traditional Chinese Medicine, State Key Laboratory Breeding Base of Systematic Research, Development and Utilization of Chinese Medicine Resources, Sichuan Province and Ministry of Science and Technology, Chengdu,China
- Department of Breast Oncology, Sun Yat-Sen University Cancer Center, State Key Laboratory of Oncology in South China, Collaborative Innovation Center for Cancer Medicine, Guangzhou,China
Keywords: Diallyl disulfide, breast cancer stem cell, CD44, PKM2, AMPK, xenograft.
Abstract: Background: It has been reported that diallyl disulfide (DADS) has anti-proliferative activity in many cancers.
Objective: The purpose of this study was to investigate the functions of DADS and the underlying mechanisms of its effect in breast cancer stem cells (BCSCs).
Method: Mammosphere formation assay, glucose consumption assay, lactate production assay and mouse xenograft experiments were performed to explore the functions of DADS in BCSCs. ATPase activity assay, western blotting and immunohistochemistry (IHC) assay were conduct to explore the mechanisms underlying the effects of DADS in BCSCs.
Results: The results showed that DADS suppressed cell stemness and glucose metabolism in BCSCs. In vivo mouse xenograft experiments showed that DADS inhibited the proliferation and metastasis of BCSCs. Then, we continued to explore the mechanisms underlying the effects of DADS in BCSCs and found that DADS acts by targeting CD44, Pyruvate kinase M2 (PKM2) and AMP-activated protein kinase (AMPK) signaling pathways. IHC analysis of 125 breast cancer patients’ tissues demonstrated that CD44, PKM2 and AMPK expression levels were positively correlated. In addition, positive CD44, PKM2 and AMPK expression was associated with poor patient overall survival (OS) and disease-free survival (DFS).
Conclusion: In summary, DADS suppresses cell stemness, proliferation, metastasis and glucose metabolism in BCSCs partly through the inhibition of CD44/PKM2/AMPK. DADS may be used as a potential therapy for breast cancer treatment.
Export Options
About this article
Cite this article as:
Xie Xinhua, Huang Xiaojia , Tang Hailin , Ye Feng, Yang Lu , Guo Xiaofang, Tian Zhi , Xie Xiaofang , Peng Cheng*, Xie Xiaoming*, Diallyl Disulfide Inhibits Breast Cancer Stem Cell Progression and Glucose Metabolism by Targeting CD44/PKM2/AMPK Signaling, Current Cancer Drug Targets 2018; 18 (6) . https://dx.doi.org/10.2174/1568009617666171024165657
DOI https://dx.doi.org/10.2174/1568009617666171024165657 |
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
-
dUTPase in Human Neoplastic Cells as a Potential Target for Therapeutic Intervention
Current Protein & Peptide Science Co-delivery Strategies Based on Multifunctional Nanocarriers for Cancer Therapy
Current Drug Metabolism Synthesis and Evaluation of Estradiol Derivatives as Anti-Breast Cancer Agents
Letters in Drug Design & Discovery Effective Inhibition of Foam Cells Formation by Tanshinone IIA in RAW264.7 Macrophages Induced with LDL Isolated from Hypercholesterolemia Patients: A Proteomic Analysis
Current Proteomics TNF-α and Ghrelin: Opposite Effects on Immune System, Metabolism and Mental Health
Protein & Peptide Letters HPV Pathway Profiling: HPV Related Cervical Dysplasia and Carcinoma Studies
Current Pharmaceutical Design Promising Anticancer Drug Candidates Based on the 7-methoxychromone Scaffold: Synthesis and Evaluation of Antiproliferative Activity
Letters in Drug Design & Discovery Selection of Lung Cancer-Specific Landscape Phage for Targeted Drug Delivery
Combinatorial Chemistry & High Throughput Screening New Opportunities for Pregnane X Receptor (PXR) Targeting in Drug Development. Lessons from Enantio- and Species-Specific PXR Ligands Identified from A Discovery Library of Amino Acid Analogues
Mini-Reviews in Medicinal Chemistry Advances in the Development of Multimodal Imaging Agents for Nuclear/Near-infrared Fluorescence Imaging
Current Medicinal Chemistry Current Development of Metal Complexes with Diamine Ligands as Potential Anticancer Agents
Current Medicinal Chemistry From Multiple PAR1 Receptor/Protein Interactions to their Multiple Therapeutic Implications
Current Topics in Medicinal Chemistry Pathogenesis of Type 1 Diabetes: Regulation of Adhesion Molecules and Immune Cell Trafficking
Current Immunology Reviews (Discontinued) Mitogen-activated Protein Kinase (MAPK) Interacting Kinases 1 and 2 (MNK1 and MNK2) as Targets for Cancer Therapy: Recent Progress in the Development of MNK Inhibitors
Current Medicinal Chemistry The Synthesis of Nano-Doxorubicin and its Anticancer Effect
Anti-Cancer Agents in Medicinal Chemistry Understanding Epithelial-Mesenchymal Transition may Reveal Novel Therapeutic Targets for Oral Squamous Cell Carcinoma
Current Cancer Therapy Reviews Working Towards the Development of Vaccines for the Treatment and Prevention of Early Breast Cancer
Current Cancer Therapy Reviews Inflammatory Cytokines in Acute Ischemic Stroke
Current Pharmaceutical Design Neuroinflamm-Aging and Neurodegenerative Diseases: An Overview
CNS & Neurological Disorders - Drug Targets A Brief Introduction to Porphyrin Compounds used in Tumor Imaging and Therapies
Mini-Reviews in Medicinal Chemistry