From the Fruit Fly to You: A Bench to Bedside
Story CHORI Group Identifies New Therapeutic Agent for Colon Cancer
CHORI scientist Julie Saba, MD, PhD, and her colleagues have just published a groundbreaking study in Cancer Research that identifies a new class of therapeutic agents that could hold the key to the prevention and treatment of colon cancer. Sphingadienes (SDs) are sphingolipid metabolites found naturally in soy that Dr. Saba’s group has found to be protective against colon cancer.
“It’s very exciting,” says Dr. Saba. “First, we are happy to find a natural molecule that could be used, or even just consumed through soy products, to help prevent colon cancer. Second, this information is important because we can build on our understanding of SDs in terms of developing new drugs to treat people who actually have colon cancer already.”
Dr. Saba’s revolutionary new study has its roots in the rather humble fruit fly.
“Studying developmental biology – the fruitfly, the worm, yeast – is often given a bad rap, but these kinds of studies can be surprisingly enlightening and clinically relevant if the investigative team approaches the research from a translational perspective,” says Dr. Saba.
That is exactly the approach Dr. Saba’s group took when they discovered that certain kinds of cells were dying in a study of the developmental biology of a mutant fruit fly with very high levels of SDs.
“Sphingolipid metabolites are small molecules in the cell that serve signaling functions in the control of life and death pathways,” explains Dr. Saba. “This means that they play a role in turning cell death on or off, which was why we were interested in their elevations being so high in this particular fruit fly.”
On further investigation, Dr. Saba discovered that they could actually use the SDs to induce cell death in the fly. When Dr. Saba’s group realized that SDs were also found in soy products, they put two and two together in a rather innovative way.
"Soy has been touted as one of the foods that may be protective against colon cancer, and there are many things in soy that could be responsible for that," Dr. Saba says.
“We suspected, however, that perhaps one of the critical components to the benefits of soy was this same family of lipids, which in this case might be inducing cell death and increasing cell turnover in the epithelial, or surface cells, of the colon.”
Although cell death does not sound like a good thing and can indeed contribute to pathology, it is also part of the normal process the body uses to remove unhealthy or mutant cells, providing what Dr. Saba refers to as a "cancer surveillance" function. Preventative colon cancer strategies often focus on the same process – ways to get rid of those cells that might be damaged – and thus more prone to turning into cancer – as quickly as possible, which was why Dr. Saba’s team was particularly interested in SDs. In a series of different experiments described in detail in the Cancer Research publication, Dr. Saba and her colleagues evaluated SDs both at the cellular level and in animal models of colon cancer with promising results.