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New Research Identifies Human Enzyme That Could Be Programmed To Kill Cancer Cells

A new study conducted by scientists at Children's Hospital Oakland Research Institute (CHORI) identifies a specific enzyme that can cause the death of cancer cells. Researchers studied 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, or S1P.

The study, led by Julie Saba, M.D., Ph.D. is the first to link the SPL enzyme to cancer, and it appears in the November issue of the Proceedings of the National Academy of Sciences. Researchers identified SPL as a key regulator of cancer cells. They discovered that if the cancer cells were stressed by chemotherapy, SPL could be activated or "turned on" 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. Approximately 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," said Dr. Saba.

Dr. Saba and her team conducted their year-long research by studying a number of different human cell lines as well as human colon cancer tissues and mouse intestinal polyps. They wanted to see what happens when you increase or decrease the activity of SPL in human cells. Their research found the enzyme makes cancer cells more vulnerable to chemotherapy, whereas 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 nearby healthy tissues. This suggests that reactivation of SPL could be used to improve cancer therapies by increasing the number of cancer cells killed by chemotherapy.

*Surveillance, Epidemiology, and End Results (SEER) Program and the American Cancer Society.

Source: Children's Hospital & Research Center at Oakland. December 2006.

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