Forum for Science, Industry and Business

Sponsored by:     3M 
Search our Site:

 

Researchers Pursue Promising New Approach in the Treatment of Liver Cancer

07.03.2012
Hepatocellular carcinoma (HCC), or primary cancer of the liver, is the fifth most common cancer worldwide.

Despite the prevalence of this disease, until now there has been no effective, systemic treatment. Thanks to a team of researchers in Boston University’s Departments of Biology and Chemistry, and the Program in Molecular Biology, Cell Biology, and Biochemistry, that may be about to change.

The BU research team and collaborators recently discovered a promising new protein target for chemotherapy in the treatment of liver cancer—the transcription factor LSF. (Transcription factors are regulatory proteins that bind genomic DNA near the start of genes, either promoting or inhibiting the transcription or copying of the gene.) LSF is found in high levels in the tumor tissue of patients with liver cancer and has been demonstrated to promote the development of cancer (oncogenesis) in studies using laboratory rodents.

Central to their findings, the BU scientists identified small molecules that effectively inhibit LSF cellular activity, which in turn slows the growth of the cancer. In particular, one such molecule, called Factor Quinolinone Inhibitor 1 (FQI1), derived from a lead compound, was found to inhibit the ability of LSF to bind DNA both in extracts (in vitro, as determined by electrophoretic mobility shift assays), and in cells. Consistent with inhibiting LSF activity, FQI1 also eliminates the ability of LSF to turn up transcription. FQI1 also demonstrates antiproliferative activity, or the ability to prevent or retard the growth of cells. While FQI1 quickly causes cell death in LSF-overexpressing cells, including liver cancer cells, healthy cells are unaffected by the treatment. This phenomenon has been called oncogene addiction, where tumor cells are “addicted” to the activity of an oncogenic factor for their survival, but normal cells can do without it. This is very encouraging for use of such compounds clinically.

Quantitative analysis of FQI1 (based on a concordant structure-activity relationship of a panel of 23 quinolinones) strongly suggests that its growth inhibitory activity focuses on a single biological target or family. This focus, coupled with the striking correlation between the concentrations required for antiproliferative activity and for inhibition of LSF transactivation indicates that LSF is that specific biological target of FQI1.

Building on the in vitro trials, the researchers tested the efficacy of FQI1 in inhibiting liver cancer tumor growth by injecting HCC cell lines into rodent models. FQI1 was observed to significantly inhibit tumor growth with no observable side effects (general tissue cytotoxicity). These dramatic findings support the further development of LSF inhibitors as a promising new chemotherapy treatment for liver cancer.

The team’s findings have been published in the article (Antiproliferative small molecule inhibitors of transcription factor LSF reveal oncogene addiction to LSF in hepatocellular carcinoma) in the Proceedings of the National Academy of Science (PNAS) (www.pnas.org/lookup/suppl/doi:10.1073/pnas.1121601109). The co-principal investigators are Ulla Hansen, Professor of Biology, and Scott Schaus, Associate Professor of Chemistry, Boston University.

Contributing authors are Trevor J. Grant, Girish Barot, Hang Gyeong Chin, Sarah Woodson, Jennifer Sherman, and Tracy Meehan, Department of Biology, Boston University; Joshua A. Bishop, Lisa M. Christadore, and John Kavouris, Department of Chemistry, Center for Chemical Methodology and Library Development at Boston University; Sriharsa Pradhan, New England BioLabs, Inc., Ipswich, MA; Ayesha Siddiq, Rachel Gredler, Xue-Ning Shen, and Devanand Sarkar, Department of Human and Molecular Genetics, Virginia Commonwealth University School of Medicine, Richmond, VA; Laura A. Briggs and William H. Andrews, Sierra Sciences, LLC, Reno, NV; and Kevin Fitzgerald, Alnylam Pharmaceuticals, Inc., Cambridge, MA.

About Boston University—Founded in 1839, Boston University is an internationally recognized private research university with more than 30,000 students participating in undergraduate, graduate, and professional programs. As Boston University’s largest academic division, the College and Graduate School of Arts & Sciences is the heart of the BU experience with a global reach that enhances the University’s reputation for teaching and research.

Contact information for the authors:

Ulla M. Hansen, Professor
Department of Biology
Boston University
5 Cummington St.
Boston, MA 02215
Office Phone (617) 353-8730
Email uhansen@bu.edu
Website www.bu.edu/biology/people/faculty/hansen/
Scott E. Schaus, Associate Professor
Department of Chemistry
Boston University
590 Commonwealth Ave.
Boston, MA 02215
Office
Phone (617) 353-2489
Email seschaus@bu.edu

Scott E. Schaus | Newswise Science News
Further information:
http://www.bu.edu

More articles from Health and Medicine:

nachricht World first: Massive thrombosis removed during early pregnancy
20.07.2017 | Universitätsspital Bern

nachricht Therapy of preterm birth in sight?
19.07.2017 | Universitätsspital Bern

All articles from Health and Medicine >>>

The most recent press releases about innovation >>>

Die letzten 5 Focus-News des innovations-reports im Überblick:

Im Focus: Manipulating Electron Spins Without Loss of Information

Physicists have developed a new technique that uses electrical voltages to control the electron spin on a chip. The newly-developed method provides protection from spin decay, meaning that the contained information can be maintained and transmitted over comparatively large distances, as has been demonstrated by a team from the University of Basel’s Department of Physics and the Swiss Nanoscience Institute. The results have been published in Physical Review X.

For several years, researchers have been trying to use the spin of an electron to store and transmit information. The spin of each electron is always coupled...

Im Focus: The proton precisely weighted

What is the mass of a proton? Scientists from Germany and Japan successfully did an important step towards the most exact knowledge of this fundamental constant. By means of precision measurements on a single proton, they could improve the precision by a factor of three and also correct the existing value.

To determine the mass of a single proton still more accurate – a group of physicists led by Klaus Blaum and Sven Sturm of the Max Planck Institute for Nuclear...

Im Focus: On the way to a biological alternative

A bacterial enzyme enables reactions that open up alternatives to key industrial chemical processes

The research team of Prof. Dr. Oliver Einsle at the University of Freiburg's Institute of Biochemistry has long been exploring the functioning of nitrogenase....

Im Focus: The 1 trillion tonne iceberg

Larsen C Ice Shelf rift finally breaks through

A one trillion tonne iceberg - one of the biggest ever recorded -- has calved away from the Larsen C Ice Shelf in Antarctica, after a rift in the ice,...

Im Focus: Laser-cooled ions contribute to better understanding of friction

Physics supports biology: Researchers from PTB have developed a model system to investigate friction phenomena with atomic precision

Friction: what you want from car brakes, otherwise rather a nuisance. In any case, it is useful to know as precisely as possible how friction phenomena arise –...

All Focus news of the innovation-report >>>

Anzeige

Anzeige

Event News

»We are bringing Additive Manufacturing to SMEs«

19.07.2017 | Event News

The technology with a feel for feelings

12.07.2017 | Event News

Leipzig HTP-Forum discusses "hydrothermal processes" as a key technology for a biobased economy

12.07.2017 | Event News

 
Latest News

Researchers create new technique for manipulating polarization of terahertz radiation

20.07.2017 | Information Technology

High-tech sensing illuminates concrete stress testing

20.07.2017 | Materials Sciences

First direct observation and measurement of ultra-fast moving vortices in superconductors

20.07.2017 | Physics and Astronomy

VideoLinks
B2B-VideoLinks
More VideoLinks >>>