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
Bioactive Polysaccharides From Natural Resources For Cancer Therapy
Bioactive polysaccharides from natural resources exhibit diverse therapeutic properties including anticancer, antioxidant, antidiabetic, immunostimulatory activity, and promotion of wound healing. In the past decades, most studies focused on the extraction and identification of polysaccharides, as well as their biological activities. A large number of bioactive polysaccharides with different structural features ...read more
Innovative Cancer Drug Targets: A New Horizon in Oncology
Cancer remains one of the most challenging diseases, with its complexity and adaptability necessitating continuous research efforts into more effective and targeted therapeutic approaches. Recent years have witnessed significant progress in understanding the molecular and genetic basis of cancer, leading to the identification of novel drug targets. These include, but ...read more
Innovative Drug Research Propelling a New Era of Precision Oncology
Drug-oncology research is leading a new era of precision medicine, becoming a frontier hotspot in cancer treatment. Advancements in molecular biology, genomics, and medicinal chemistry have driven revolutionary changes in cancer cognition and treatment strategies. Gene-targeted drugs provide more precise treatments, improving survival rates for certain cancers. Network pharmacology offers ...read more
Novel Targets in Cancer Immunotherapy
Cancer immunotherapy, particularly immune checkpoint inhibitors (ICIs), has greatly revolutionized therapeutic strategies in the field of cancer. Current targets of FDA-approved ICIs include CTLA-4, PD-1/PDl-1, and LAG-3. However, the prognosis of cancer patients, especially with solid tumors, remains unfavorable due to the intrinsic and acquired resistance. For the past decades, ...read more

- Author Guidelines
- Bentham Author Support Services (BASS)
- 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
-
It Takes Two to Tango: The Structure and Function of LIM, RING, PHD and MYND Domains
Current Pharmaceutical Design Current Status of the Non-nucleoside Reverse Transcriptase Inhibitors of Human Immunodeficiency Virus Type 1
Current Topics in Medicinal Chemistry Somatostatin and Octreotide on the Treatment of Acute Pancreatitis - Basic and Clinical Studies for Three Decades
Current Pharmaceutical Design Advanced Assessment of the Endogenous Hormone Level as a Potential Biomarker of the Urogenital Tract Cancer
Combinatorial Chemistry & High Throughput Screening Plasticity of T Cell Differentiation and Cytokine Signature: A Double-Edged Sword for Immune Responses
Immunology, Endocrine & Metabolic Agents in Medicinal Chemistry (Discontinued) Turning Tumor-Promoting Copper into an Anti-Cancer Weapon via High-Throughput Chemistry
Current Medicinal Chemistry Cancer “Stemness”- Regulating MicroRNAs: Role, Mechanisms and Therapeutic Potential
Current Drug Targets miRNA: Small Molecules as Potential Novel Biomarkers in Cancer
Current Medicinal Chemistry An Update on Natural Occurrence and Biological Activity of Chromones
Current Medicinal Chemistry A 1536-Well Fluorescence Polarization Assay to Screen for Modulators of the MUSASHI Family of RNA-Binding Proteins
Combinatorial Chemistry & High Throughput Screening New Trends in Anti-Cancer Therapy: Combining Conventional Chemotherapeutics with Novel Immunomodulators
Current Medicinal Chemistry The Molecular Basis of Notch Signaling Regulation: A Complex Simplicity
Current Molecular Medicine Aberrant Regulation of Translation Initiation in Tumorigenesis
Current Molecular Medicine IAPs as a Target for Anticancer Therapy
Current Cancer Drug Targets Factors Controlling Chromatin Organization and Nucleosome Positioning for Establishment and Maintenance of HIV Latency
Current HIV Research Eosinophils in Cancer: Favourable or Unfavourable?
Current Medicinal Chemistry Biology and Impact of Signal Transducers and Activators of Transcription and Their Regulators as Targets in Cancer Therapy
Current Signal Transduction Therapy Tyrosine Kinase Inhibitor as a new Therapy for Ischemic Stroke and other Neurologic Diseases: is there any Hope for a Better Outcome?
Current Neuropharmacology Glycerophospholipid Synthesis as a Novel Drug Target Against Cancer
Current Molecular Pharmacology Activated Cancer Therapy Using Light and Ultrasound - A Case Series of Sonodynamic Photodynamic Therapy in 115 Patients Over a 4 Year Period
Current Drug Therapy