Human Enzyme Programmed to Destroy Cancer Cells

Researchers evaluated the behavior of an enzyme called sphingosine phosphate lyase (SPL), which can regulate cell growth and death by lowering the levels of a natural, growth-promoting lipid called sphingosine-1-phosphate (S1P).

The study, led by Julie Saba, M.D., Ph.D., from Children's Hospital Oakland Research Institute (CHORI; Oakland, CA, USA), is the first to tie the SPL enzyme to cancer, and was published in the November 2006 issue of the journal Proceedings of the [U.S.] National Academy of Sciences. Researchers identified SPL as a major regulator of cancer cells. They found that if the cancer cells were stressed by chemotherapy, SPL could be activated to reduce the levels of S1P, which is needed to cause cell death.

"The enzyme SPL senses when a cell has sustained damage or is undergoing mutations,” said Dr. Saba. "Once the enzyme is aware of these changes it responds by killing the cell. We hope to find new ways to leverage the body's own natural responses to these mutated or damaged cells to target cancer cells.”

Among pediatric diseases, cancer is the leading cause of death in the United States. About 9,500 new cases of cancer are expected to occur in children between infancy and 15 years of age by the end 2006. "Although we're beginning our studies in colon cancer, we believe our research findings will have a direct impact on investigations for other cancers, including pediatric cancers,” said Dr. Saba. "It is premature to suggest that SPL is the answer to curing cancer, but our research findings should dramatically advance our search for a cure.”

Dr. Saba and her colleagues conducted their year-long research by assessing a variety of different human cell lines as well as human colon cancer tissues and mouse intestinal polyps. They tried to determine what occurs when the activity of SPL is increased or decrease in human cells. Their study discovered that the enzyme makes cancer cells more susceptible to chemotherapy, while removing the enzyme makes the cells more resistant to treatment. They also found that the enzyme is inactive in colon cancers and mouse polyps, but very active in neighboring healthy tissues.

The researchers concluded that this suggests that reactivation of SPL could be utilized to improve cancer therapies by increasing the number of cancer cells killed by chemotherapy.



Related Links:
Children's Hospital Oakland Research Institute