Abstract
Hydroxytyrosol, an important polyphenolic compound found in olive oil, has shown anti-tumor activity both in vitro and in vivo. However, effects of hydroxytyrosol on prostate cancer are largely unkown. We found that hydroxytyrosol preferentially reduces the viability of human prostate cancer cells (PC-3, DU145) compared to an immortalized non-malignant prostate epithelial cell line (RWPE-1). Exposure of PC-3 cells to 80 µmol/L hydroxytyrosol resulted in significant increases in both superoxide production and activation of apoptosis. These increases were accompanied by mitochondrial dysfunction, defects in autophagy, and activation of MAP kinases. Moreover, N-acetylcysteine (NAC), an efficient reactive oxygen species (ROS) scavenger, was able to reverse the hydroxytyrosol-induced effects of cell viability loss, defects in autophagy, and activation of apoptosis. This evidence suggests that ROS play a vital role in the loss of PC-3 cell viability. However, MAPK inhibitors including U0126 (for Erk1/2), SB203580 (for p38MAPK) and SP600125 (for JNK) did not decrease hydroxytyrosol-induced growth inhibition, suggesting that these kinases may not be required for the growth inhibitory effect of hydroxytyrosol. Moreover, addition of ROS scavengers (i.e. NAC, catalase, pyruvate, SOD) in the growth media can prevent hydroxytyrosol induced cell viability loss, suggesting that extracellular ROS (superoxide and hydrogen peroxide) facilitate the anti-proliferation effect of hydroxytyrosol in prostate cancer cells. The present work firstly shows that hydroxytyrosol induces apoptotic cell death and mitochondrial dysfunction by generating superoxide in PC-3 cells. This research presents preliminary evidence on the in vitro chemopreventive effect of hydroxytyrosol, and will contribute to further investigation of hydroxytyrosol as an anti-cancer agent.
Keywords: Autophagy, hydroxytyrosol, mitochondrial dysfunction, prostate cancer, superoxide.
Current Cancer Drug Targets
Title:Hydroxytyrosol Promotes Superoxide Production and Defects in Autophagy Leading to Anti-proliferation and Apoptosis on Human Prostate Cancer Cells
Volume: 13 Issue: 6
Author(s): Cheng Luo, Yan Li, Hui Wang, Yang Cui, Zhihui Feng, Hua Li, Yuan Li, Ying Wang, Karin Wurtz, Peter Weber, Jiangang Long and Jiankang Liu
Affiliation:
Keywords: Autophagy, hydroxytyrosol, mitochondrial dysfunction, prostate cancer, superoxide.
Abstract: Hydroxytyrosol, an important polyphenolic compound found in olive oil, has shown anti-tumor activity both in vitro and in vivo. However, effects of hydroxytyrosol on prostate cancer are largely unkown. We found that hydroxytyrosol preferentially reduces the viability of human prostate cancer cells (PC-3, DU145) compared to an immortalized non-malignant prostate epithelial cell line (RWPE-1). Exposure of PC-3 cells to 80 µmol/L hydroxytyrosol resulted in significant increases in both superoxide production and activation of apoptosis. These increases were accompanied by mitochondrial dysfunction, defects in autophagy, and activation of MAP kinases. Moreover, N-acetylcysteine (NAC), an efficient reactive oxygen species (ROS) scavenger, was able to reverse the hydroxytyrosol-induced effects of cell viability loss, defects in autophagy, and activation of apoptosis. This evidence suggests that ROS play a vital role in the loss of PC-3 cell viability. However, MAPK inhibitors including U0126 (for Erk1/2), SB203580 (for p38MAPK) and SP600125 (for JNK) did not decrease hydroxytyrosol-induced growth inhibition, suggesting that these kinases may not be required for the growth inhibitory effect of hydroxytyrosol. Moreover, addition of ROS scavengers (i.e. NAC, catalase, pyruvate, SOD) in the growth media can prevent hydroxytyrosol induced cell viability loss, suggesting that extracellular ROS (superoxide and hydrogen peroxide) facilitate the anti-proliferation effect of hydroxytyrosol in prostate cancer cells. The present work firstly shows that hydroxytyrosol induces apoptotic cell death and mitochondrial dysfunction by generating superoxide in PC-3 cells. This research presents preliminary evidence on the in vitro chemopreventive effect of hydroxytyrosol, and will contribute to further investigation of hydroxytyrosol as an anti-cancer agent.
Export Options
About this article
Cite this article as:
Luo Cheng, Li Yan, Wang Hui, Cui Yang, Feng Zhihui, Li Hua, Li Yuan, Wang Ying, Wurtz Karin, Weber Peter, Long Jiangang and Liu Jiankang, Hydroxytyrosol Promotes Superoxide Production and Defects in Autophagy Leading to Anti-proliferation and Apoptosis on Human Prostate Cancer Cells, Current Cancer Drug Targets 2013; 13 (6) . https://dx.doi.org/10.2174/15680096113139990035
DOI https://dx.doi.org/10.2174/15680096113139990035 |
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
-
Histone Deacetylase Inhibitors: From Chromatin Remodeling to Experimental Cancer Therapeutics
Current Medicinal Chemistry Molecular and Biological Functions of Melatonin in Endometrial Cancer
Current Drug Targets Therapeutic Agents Based on DNA Sequence Specific Binding
Current Topics in Medicinal Chemistry Mechanisms of Tubulin Binding Ligands to Target Cancer Cells: Updates on their Therapeutic Potential and Clinical Trials
Current Cancer Drug Targets Advanced Methods for the Analysis of Testosterone
Current Medicinal Chemistry Functional Genomics Approaches in Cancer Research
Current Genomics Denosumab: The Era of Targeted Therapies in Bone Metastatic Diseases
Current Cancer Drug Targets Ontologies of Drug Discovery and Design for Neurology, Cardiology and Oncology
Current Pharmaceutical Design Heat Shock Proteins: A Potential Anticancer Target
Current Drug Targets The Expanding Universe of γ δ T Lymphocytes: Subsets, Generation and Function
Current Immunology Reviews (Discontinued) Notch Inhibitors as a New Tool in the War on Cancer: A Pathway to Watch
Current Pharmaceutical Biotechnology Colchicine: An Ancient Drug with Multiple Benefits
Current Pharmaceutical Design The Effect of Psychological Stress and Social Isolation on Neuroimmunoendocrine Communication
Current Pharmaceutical Design Dynamic Contrast-Enhanced Magnetic Resonance Imaging for Differentiating Between Primary Tumor, Metastatic Node and Normal Tissue in Head and Neck Cancer
Current Medical Imaging Anticancer Potential and Molecular Targets of Pristimerin: A Mini- Review
Current Cancer Drug Targets Recent Advances In Developing Novel Anti-Cancer Drugs Targeting Tumor Hypoxic and Acidic Microenvironments
Recent Patents on Anti-Cancer Drug Discovery The Central Role of Angiotensin I-Converting Enzyme in Vertebrate Pathophysiology
Current Topics in Medicinal Chemistry Molecular Targeting of Acid Ceramidase: Implications to Cancer Therapy
Current Drug Targets Metabolic and Amino Acid Alterations of the Tumor Microenvironment
Current Medicinal Chemistry Clinical Applications of the Urokinase Receptor (uPAR) for Cancer Patients
Current Pharmaceutical Design