Histone Deacetylase Inhibitors Boost Parvovirus Cancer Killing Action
By LabMedica International staff writers Posted on 28 Oct 2013 |

Image: Computer-generated representation of parvovirus H-1 (H-1PV) (Photo courtesy of Dr. Antonio Marchini, German Cancer Research Center).
The anticancer action of parvoviruses can be dramatically improved by co-treating cancer cells with parvovirus and histone deacetylase inhibitors (HDACIs) such as valproic acid.
The rat parvovirus H-1PV has oncolytic and tumor-suppressive properties potentially exploitable in cancer therapy. This possibility is being explored by cancer researchers, and while results have been encouraging, they have found that it is necessary to improve the cancer-killing capability of the virus.
Towards this end, investigators at the German Cancer Research Center (Heidelberg) have sought drugs or drug combinations that would improve the ability of parvoviruses to kill cancer cells. In a paper published in the September 17, 2013, online edition of the journal EMBO Molecular Medicine they described the effect of the histone deacetylase inhibitor valproic acid (VPA) on the interaction between H-1PV and human cervical carcinoma and pancreatic carcinoma cell lines.
The investigators showed that co-treatment of cultures with the parvovirus and VPA boosted the ability of the virus to kill a range of human cervical carcinoma and pancreatic carcinoma cell lines by inducing oxidative stress, DNA damage, and apoptosis. Furthermore, in rat and mouse xenograft models, H-1PV/VPA co-treatment strongly inhibited tumor growth promoting complete tumor remission in all co-treated animals. In contrast, animals treated with the same virus dose without the drug displayed no regression, not even when a 20-times higher dose of viruses was administered.
At the molecular level, the investigators found that the parvovirus nonstructural protein NS1 modulated viral transcription and cytotoxicity, both of which were enhanced by VPA treatment. NS1 was acetylated at residues K85 and K257 and addition of VPA correlated with an enhanced rate of NS1 acetylation. In contrast, amino-acid substitution of the two acetylation sites strongly impaired NS1-mediated viral gene transcription, viral replication, and cytotoxicity. VPA induced hyper-acetylation of NS1, which converted the protein into a more active polypeptide.
"The synergistic effect of a combination of parvoviruses and valproic acid enables us to deliver both the viruses and the drug at low doses, which prevents severe side effects," said senior author Dr. Antonio Marchini, a principle investigator in virology at the German Cancer Research Center. "The results are encouraging us to carry out further tests of this combination therapy. We believe it has the potential to arrest tumor growth in severe cases of cancer. We obtained impressive results in preclinical trials with parvovirus H-1 in brain tumors. However, the oncolytic effect of the viruses is weaker in other cancers. Therefore, we are searching for ways to increase the therapeutic potential of the viruses."
Related Links:
German Cancer Research Center
The rat parvovirus H-1PV has oncolytic and tumor-suppressive properties potentially exploitable in cancer therapy. This possibility is being explored by cancer researchers, and while results have been encouraging, they have found that it is necessary to improve the cancer-killing capability of the virus.
Towards this end, investigators at the German Cancer Research Center (Heidelberg) have sought drugs or drug combinations that would improve the ability of parvoviruses to kill cancer cells. In a paper published in the September 17, 2013, online edition of the journal EMBO Molecular Medicine they described the effect of the histone deacetylase inhibitor valproic acid (VPA) on the interaction between H-1PV and human cervical carcinoma and pancreatic carcinoma cell lines.
The investigators showed that co-treatment of cultures with the parvovirus and VPA boosted the ability of the virus to kill a range of human cervical carcinoma and pancreatic carcinoma cell lines by inducing oxidative stress, DNA damage, and apoptosis. Furthermore, in rat and mouse xenograft models, H-1PV/VPA co-treatment strongly inhibited tumor growth promoting complete tumor remission in all co-treated animals. In contrast, animals treated with the same virus dose without the drug displayed no regression, not even when a 20-times higher dose of viruses was administered.
At the molecular level, the investigators found that the parvovirus nonstructural protein NS1 modulated viral transcription and cytotoxicity, both of which were enhanced by VPA treatment. NS1 was acetylated at residues K85 and K257 and addition of VPA correlated with an enhanced rate of NS1 acetylation. In contrast, amino-acid substitution of the two acetylation sites strongly impaired NS1-mediated viral gene transcription, viral replication, and cytotoxicity. VPA induced hyper-acetylation of NS1, which converted the protein into a more active polypeptide.
"The synergistic effect of a combination of parvoviruses and valproic acid enables us to deliver both the viruses and the drug at low doses, which prevents severe side effects," said senior author Dr. Antonio Marchini, a principle investigator in virology at the German Cancer Research Center. "The results are encouraging us to carry out further tests of this combination therapy. We believe it has the potential to arrest tumor growth in severe cases of cancer. We obtained impressive results in preclinical trials with parvovirus H-1 in brain tumors. However, the oncolytic effect of the viruses is weaker in other cancers. Therefore, we are searching for ways to increase the therapeutic potential of the viruses."
Related Links:
German Cancer Research Center
Latest BioResearch News
- Genome Analysis Predicts Likelihood of Neurodisability in Oxygen-Deprived Newborns
- Gene Panel Predicts Disease Progession for Patients with B-cell Lymphoma
- New Method Simplifies Preparation of Tumor Genomic DNA Libraries
- New Tool Developed for Diagnosis of Chronic HBV Infection
- Panel of Genetic Loci Accurately Predicts Risk of Developing Gout
- Disrupted TGFB Signaling Linked to Increased Cancer-Related Bacteria
- Gene Fusion Protein Proposed as Prostate Cancer Biomarker
- NIV Test to Diagnose and Monitor Vascular Complications in Diabetes
- Semen Exosome MicroRNA Proves Biomarker for Prostate Cancer
- Genetic Loci Link Plasma Lipid Levels to CVD Risk
- Newly Identified Gene Network Aids in Early Diagnosis of Autism Spectrum Disorder
- Link Confirmed between Living in Poverty and Developing Diseases
- Genomic Study Identifies Kidney Disease Loci in Type I Diabetes Patients
- Liquid Biopsy More Effective for Analyzing Tumor Drug Resistance Mutations
- New Liquid Biopsy Assay Reveals Host-Pathogen Interactions
- Method Developed for Enriching Trophoblast Population in Samples
Channels
Clinical Chemistry
view channel
New Clinical Chemistry Analyzer Designed to Meet Growing Demands of Modern Labs
A new clinical chemistry analyzer is designed to provide outstanding performance and maximum efficiency, without compromising affordability, to meet the growing demands of modern laboratories.... Read more
New Reference Measurement Procedure Standardizes Nucleic Acid Amplification Test Results
Nucleic acid amplification tests (NAATs) play a key role in diagnosing a wide range of infectious diseases. These tests are generally known for their high sensitivity and specificity, and they can be developed... Read moreMolecular Diagnostics
view channel
RNA-Seq Based Diagnostic Test Enhances Diagnostic Accuracy of Pediatric Leukemia
A new unique test is set to reshape the way Acute Lymphoblastic Leukemia (BCP-ALL) samples can be analyzed. Qlucore (Lund, Sweden) has launched the first CE-marked RNA-seq based diagnostic test for pediatric... Read more
New Technique for Measuring Acidic Glycan in Blood Simplifies Schizophrenia Diagnosis
Polysialic acid is a unique acidic glycan predominantly found in brain regions associated with memory and emotion, but it is also present in the bloodstream. Research has shown that blood levels of polysialic... Read moreHematology
view channel
Disposable Cartridge-Based Test Delivers Rapid and Accurate CBC Results
Complete Blood Count (CBC) is one of the most commonly ordered lab tests, crucial for diagnosing diseases, monitoring therapies, and conducting routine health screenings. However, more than 90% of physician... Read more
First Point-of-Care Heparin Monitoring Test Provides Results in Under 15 Minutes
Heparin dosing requires careful management to avoid both bleeding and clotting complications. In high-risk situations like extracorporeal membrane oxygenation (ECMO), mortality rates can reach about 50%,... Read moreImmunology
view channel
Blood Test Detects Organ Rejection in Heart Transplant Patients
Following a heart transplant, patients are required to undergo surgical biopsies so that physicians can assess the possibility of organ rejection. Rejection happens when the recipient’s immune system identifies... Read more
Liquid Biopsy Approach to Transform Diagnosis, Monitoring and Treatment of Lung Cancer
Lung cancer continues to be a major contributor to cancer-related deaths globally, with its biological complexity and diverse regulatory processes making diagnosis and treatment particularly difficult.... Read more
Computational Tool Exposes Hidden Cancer DNA Changes Influencing Treatment Resistance
Structural changes in tumor DNA are among the most damaging genetic alterations in cancer, yet they often go undetected, particularly when tissue samples are degraded or of low quality. These hidden genomic... Read moreMicrobiology
view channel
Viral Load Tests Can Help Predict Mpox Severity
Mpox is a viral infection that causes flu-like symptoms and a characteristic rash, which evolves significantly over time and varies between patients. The disease spreads mainly through direct contact with... Read more
Gut Microbiota Analysis Enables Early and Non-Invasive Detection of Gestational Diabetes
Gestational diabetes mellitus is a common metabolic disorder marked by abnormal glucose metabolism during pregnancy, typically emerging in the mid to late stages. It significantly heightens the risk of... Read morePathology
view channel
AI Performs Virtual Tissue Staining at Super-Resolution
Conventional histopathology, essential for diagnosing various diseases, typically involves chemically staining tissue samples to reveal cellular structures under a microscope. This process, known as “histochemical... Read more
AI-Driven Preliminary Testing for Pancreatic Cancer Enhances Prognosis
Pancreatic cancer poses a major global health threat due to its high mortality rate, with 467,409 deaths and 510,992 new cases reported worldwide in 2022. Often referred to as the "king" of all cancers,... Read more
Cancer Chip Accurately Predicts Patient-Specific Chemotherapy Response
Esophageal adenocarcinoma (EAC), one of the two primary types of esophageal cancer, ranks as the sixth leading cause of cancer-related deaths worldwide and currently lacks effective targeted therapies.... Read more
Clinical AI Solution for Automatic Breast Cancer Grading Improves Diagnostic Accuracy
Labs that use traditional image analysis methods often suffer from bottlenecks and delays. By digitizing their pathology practices, labs can streamline their work, allowing them to take on larger caseloads... Read moreTechnology
view channel
Inexpensive DNA Coated Electrode Paves Way for Disposable Diagnostics
Many people around the world still lack access to affordable, easy-to-use diagnostics for diseases like cancer, HIV, and influenza. Conventional sensors, while accurate, often rely on expensive equipment... Read more
New Miniature Device to Transform Testing of Blood Cancer Treatments
Chimeric antigen receptor (CAR) T cell therapy has emerged as a groundbreaking treatment for blood cancers like leukemia, offering hope to patients when other treatments fail. However, despite its promise,... Read moreIndustry
view channel
Lunit and Microsoft Collaborate to Advance AI-Driven Cancer Diagnosis
Lunit (Seoul, South Korea) and Microsoft (Redmond, WA, USA) have entered into a collaboration to accelerate the delivery of artificial intelligence (AI)-powered healthcare solutions. In conjunction with... Read more