Abstract
Heat shock protein 32 (Hsp32), also known as heme oxygenase-1 (HO-1), is a stress-related anti-apoptotic molecule, that has been implicated in enhanced survival of neoplastic cells and in drug-resistance. We here show that Hsp32 is expressed in most solid tumors and hematopoietic neoplasms and may be employed as a new therapeutic target as evidenced by experiments using specific siRNA and a Hsp32-targeting pharmacologic inhibitor. This Hsp-32 targeting drug, SMA-ZnPP, was found to inhibit the proliferation of neoplastic cells with IC50 values ranging between 1 and 50 μM. In addition, SMA-ZnPP induced apoptosis in all neoplastic cells examined. Furthermore, SMA-ZnPP was found to synergize with other targeted and conventional drugs in producing growth-inhibition. Resulting synergistic effects were observed in all tumor- and leukemia cells examined. Interestingly, several of the drug partners, when applied as single agents, induced the expression of Hsp32 in neoplastic cells, suggesting that synergistic effects resulted from SMA-ZnPPinduced ablation of a Hsp32-mediated survival-pathway that is otherwise used by tumor cells to escape drug induced apoptosis. Together, Hsp32 is an important survival factor and target in solid tumors and hematopoietic neoplasms, and may be used to optimize anticancer therapy by combining conventional or targeted drugs with Hsp32-inhibitors. Based on these data, it seems desirable to explore the value of Hsp32-targeting drugs as anti-cancer agents in clinical trials.
Keywords: Solid tumors, Leukemias, HO-1, Hsp32, SMA-ZnPP, targeted drugs
Current Cancer Drug Targets
Title: Targeting of Hsp32 in Solid Tumors and Leukemias: A Novel Approach to Optimize Anticancer Therapy (Supplementry Material)
Volume: 9 Issue: 5
Author(s): A. K. Iyer, P. Valent, C. Zielinski, H. Maeda, C. Sillaber, R. Panzer-Grumayer, B. Marian, W. F. Pickl, M.-T. Krauth, K. V. Gleixner, H. Herrmann, E. Hadzijusufovic, E. Lackner, S. Cerny-Reiterer, G. Hormann, A. Gruze, A. Vales and M. Mayerhofer
Affiliation:
Keywords: Solid tumors, Leukemias, HO-1, Hsp32, SMA-ZnPP, targeted drugs
Abstract: Heat shock protein 32 (Hsp32), also known as heme oxygenase-1 (HO-1), is a stress-related anti-apoptotic molecule, that has been implicated in enhanced survival of neoplastic cells and in drug-resistance. We here show that Hsp32 is expressed in most solid tumors and hematopoietic neoplasms and may be employed as a new therapeutic target as evidenced by experiments using specific siRNA and a Hsp32-targeting pharmacologic inhibitor. This Hsp-32 targeting drug, SMA-ZnPP, was found to inhibit the proliferation of neoplastic cells with IC50 values ranging between 1 and 50 μM. In addition, SMA-ZnPP induced apoptosis in all neoplastic cells examined. Furthermore, SMA-ZnPP was found to synergize with other targeted and conventional drugs in producing growth-inhibition. Resulting synergistic effects were observed in all tumor- and leukemia cells examined. Interestingly, several of the drug partners, when applied as single agents, induced the expression of Hsp32 in neoplastic cells, suggesting that synergistic effects resulted from SMA-ZnPPinduced ablation of a Hsp32-mediated survival-pathway that is otherwise used by tumor cells to escape drug induced apoptosis. Together, Hsp32 is an important survival factor and target in solid tumors and hematopoietic neoplasms, and may be used to optimize anticancer therapy by combining conventional or targeted drugs with Hsp32-inhibitors. Based on these data, it seems desirable to explore the value of Hsp32-targeting drugs as anti-cancer agents in clinical trials.
Export Options
About this article
Cite this article as:
Iyer K. A., Valent P., Zielinski C., Maeda H., Sillaber C., Panzer-Grumayer R., Marian B., Pickl F. W., Krauth M.-T., Gleixner V. K., Herrmann H., Hadzijusufovic E., Lackner E., Cerny-Reiterer S., Hormann G., Gruze A., Vales A. and Mayerhofer M., Targeting of Hsp32 in Solid Tumors and Leukemias: A Novel Approach to Optimize Anticancer Therapy (Supplementry Material), Current Cancer Drug Targets 2009; 9 (5) . https://dx.doi.org/10.2174/156800909789057024
DOI https://dx.doi.org/10.2174/156800909789057024 |
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
-
The MYC Oncogene as a Cancer Drug Target
Current Cancer Drug Targets The Role of STAT3 Signaling in Mediating Tumor Resistance to Cancer Therapy
Current Drug Targets Kit: Molecule of Interest for the Diagnosis and Treatment of Mastocytosis and other Neoplastic Disorders
Current Cancer Drug Targets Signal Transduction Pathways and Transcription Factors as Therapeutic Targets in Inflammatory Disease: Towards Innovative Antirheumatic Therapy
Current Pharmaceutical Design The Transcription Factor ETS-1: Its Role in Tumour Development and Strategies for its Inhibition
Mini-Reviews in Medicinal Chemistry Doxycycline in Mitochondrial Mediated Pathway of Apoptosis: A Systematic Review
Anti-Cancer Agents in Medicinal Chemistry Stem Cell Defects in Philadelphia Chromosome Negative Chronic Myeloproliferative Disorders: A Phenotypic and Molecular Puzzle?
Current Stem Cell Research & Therapy HDAC as a Therapeutic Target for Treatment of Endometrial Cancers
Current Pharmaceutical Design Overcoming Drug Resistance by Enhancing Apoptosis of Tumor Cells
Current Cancer Drug Targets Retinoids as Critical Modulators of Immune Functions: New Therapeutic Perspectives for Old Compounds
Endocrine, Metabolic & Immune Disorders - Drug Targets Novel Approaches for RNA Interference and their Application in Cancer Therapy
Current Pharmacogenomics Chemical Advances in Therapeutic Application of Exosomes and Liposomes
Current Medicinal Chemistry Chlorambucil Cytotoxicity Reduction in Rats Through Bone Marrow, An In vivo Study
Anti-Cancer Agents in Medicinal Chemistry Electrochemical Study of Ellipticine Interaction with Single and Double Stranded Oligonucleotides
Anti-Cancer Agents in Medicinal Chemistry Chalcone Derivatives Activate and Desensitize the Transient Receptor Potential Ankyrin 1 Cation Channel, Subfamily A, Member 1 TRPA1 Ion Channel: Structure-Activity Relationships in vitro and Anti-Nociceptive and Anti-inflammatory Activity in vivo
CNS & Neurological Disorders - Drug Targets Molecular Imaging of Matrix Metalloproteinases In Vivo Using Small Molecule Inhibitors for SPECT and PET
Current Medicinal Chemistry Phytochemistry and Pharmacognosy of Naturally Occurring Prenyloxyanthraquinones
Current Drug Targets Paraneoplastic Pemphigus: Autoimmune-Cancer Nexus in the Skin
Anti-Cancer Agents in Medicinal Chemistry Molecular Advances Toward the Understanding of the Patho-Biology of Idiopathic Myelofibrosis
Current Immunology Reviews (Discontinued) Down-Regulation of Notch1 Expression is Involved in HL-60 Cell Growth Inhibition Induced by 4-Hydroxynonenal, a Product of Lipid Peroxidation
Medicinal Chemistry