S1P Gene Regulating Lipid May Help Develop New Drugs against Cancer
Shingosine-1-phosphate (S1P) represents a bioactive lipid messenger which can be found in our blood in large quantities. A team of scientists from the Virginia Commonwealth University School of Medicine observed that this lipid has an important role in developing a new type of drugs that counteract cancer and inflammatory.
This study is published in journal Science in the September issue. The research team was composed of: Nitai Hait, Jeremy Allegood, Michael Maceyka, Graham Strub, Kuzhuvelil Harikumar, Sandeep Singh, Tomasz Kordula, Cheng Luo, Ronen Marmorstein, Sheldon Milstien. They were led in their studies by Professor Sarah Spiegel from Virginia Commonwealth University, Biochemistry and Molecular Biology Department. The costs of the research were supported in the form of a grant received from the National Institutes of Health.
Professor Spiegel is well-known for innovative work regarding newly discovered lipid mediators, even though the scope of S1P concerned with cellular development was discovered almost ten years ago. The nuclei of the cells produce and comprise Shingosine-1-phosphate. Knowing that the nucleus of a cell also contains DNA which encrypts the genetic material of every being, S1P also plays a great role in regulating some specific genes. The researchers uncovered the methods by which cancer infected cells generate Shingosine-1-phosphate and discovered the lipid`s role in regulating the gene expression.
Conducting their research, the scientists proved that Shingosine-1-phosphate is produced by sphingosine kinase type 2 found in the nucleus of a cell. The bioactive lipid behaves like a chemotherapeutic drug and fights against cancer by regulation of the genes. S1P has the characteristics of histone deacetylase inhibitors. These complexes of enzymes have the capacity to regulate a large number of gene expressions that encrypt the proteins concerned with cancer and a significant number of other diseases in human beings. Even though the physiological regulators of the histone deacetylase inhibitors are unknown, these families of enzymes can be found in some clinical trials. As Professor Spiegel, lead author of the study states: “Our work shows that S1P is a physiologically important regulator of histone deacetylases. We believe that our studies will help in the development of a new class of histone deacetylase inhibitors that might be useful for treatment of cancer and inflammatory diseases.”
The team of researchers discovered before this study that type 1 sphingosine kinase also produces Shingosine-1-phosphate but unlike type 2 sphingosine kinase, the type one variant produces the bioactive lipid outside its nucleus. Moreover, this type of sphingosine kinase has disappointing results when it comes to numerous types of human cancers. The researchers managed to develop an inhibitor for type 1 sphingosine kinase which, during clinical trials, proved to be very effective in mice. The inhibitor was very efficient in counteracting brain cancer tumors and leukemia, and the scientists believe it to be the same in the case of human illnesses.
