Features Partner Sites Information LinkXpress
Sign In
Advertise with Us
RANDOX LABORATORIES

Events

06 Jun 2016 - 09 Jun 2016
22 Jun 2016 - 24 Jun 2016
04 Jul 2016 - 06 Jul 2016

Histone Deacetylase Inhibitors Boost Parvovirus Cancer Killing Action

By BiotechDaily International staff writers
Posted on 28 Oct 2013
Print article
Image: Computer-generated representation of parvovirus H-1 (H-1PV) (Photo courtesy of Dr. Antonio Marchini, German Cancer Research Center).
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



Print article

Channels

Drug Discovery

view channel

Experimental Small-Molecule Anticancer Drug Blocks RAS-binding Domains

The experimental small-molecule anticancer drug rigosertib was shown to block tumor growth by acting as an RAS-mimetic and interacting with the RAS binding domains of RAF kinases, resulting in their inability to bind to RAS, which inhibited the RAS-RAF-MEK pathway. Oncogenic activation of RAS genes due to point mutations... Read more

Biochemistry

view channel
Image: A space-filling model of the anticonvulsant drug carbamazepine (Photo courtesy of Wikimedia Commons).

Wastewater May Contaminate Crops with Potentially Dangerous Pharmaceuticals

Reclaimed wastewater used to irrigate crops is contaminated with pharmaceutical residues that can be detected in the urine of those who consumed such produce. Investigators at the Hebrew University... Read more

Lab Technologies

view channel

Huge Modifiable Biomedical Database to Be Available on the Wikidata Site

Genome researchers are exploiting the power of the open Internet community Wikipedia database to create a comprehensive resource for geneticists, molecular biologists, and other interested life scientists. While efficiency in generating scientific data improves almost daily, applying meaningful relationships between... Read more

Business

view channel

European Biotech Agreement to Promote Antigen-Drug Conjugation Technology

Two European biotech companies have joined forces to exploit and commercialize an innovative, site-specific ADC (antigen-drug conjugate) conjugation technology. ProBioGen (Berlin, Germany), a company specializing in the development and manufacture of complex glycoproteins and Eucodis Bioscience (Vienna, Austria), a... Read more
Copyright © 2000-2016 Globetech Media. All rights reserved.