"These compounds our team found are the first 'drug-like' agents that have been shown to inhibit an enzyme called sphingosine kinase," said Charles D. Smith, Ph.D., professor of pharmacology, and director of the Drug Discovery Core, Penn State College of Medicine. "Since sphingosine kinase is involved in growth regulation and certain other biological processes that are important in tumor growth, these compounds have potential use for the treatment of many types of cancer."
This study, titled, "Discovery and evaluation of inhibitors of human sphingosine kinase," appeared in the Sept. 15 issue of Cancer Research and was recently presented at two international scientific meetings. Smith's research team in the Department of Pharmacology included: Kevin J. French, Ph.D., Randy Schrecengost, Brian D. Lee, Yan Zhuang, Ph.D., Staci N. Smith, Justin L. Eberly, and Jong K. Yun, Ph.D., of the Jake Gittlen Cancer Research Institute.
Previous studies have shown that sphingosine kinase (SK) plays a pivotal role in regulating cell growth. Cell membranes contain sphingomyelin, a precursor of two lipids: ceramide, which causes programmed cell death (apoptosis), and sphingosine 1-phosphate (S1P), which causes cell proliferation. The balance of ceramide and S1P determine whether cells multiply or die.
A chain reaction with other enzymes can turn ceramide into sphingosine, which then reacts with SK to form S1P. This promotes cell proliferation, and stops the programmed cell death that would otherwise rid the body of the cancer cells. This study aimed to find a way to stop that chain reaction and create an effective option to treat cancer.
In this project, the Smith team first determined that the amount of mRNA for SK is significantly higher in tumor cells than it is in healthy cells. mRNA is genetic material that holds the informat
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Contact: Valerie Gliem
vgliem@psu.edu
814-865-9481
Penn State
15-Sep-2003