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Researchers from VCU Massey Comprehensive Cancer Center recently demonstrated that the inhibition of glucosylceramide synthase (GCS) can cause death in cancer cells that is independent of changes in pro-death ceramide levels. The findings, which were recently published in Cell Death Discovery, showed that using eliglustat, an FDA-approved drug, induced cell death in several cancer cell lines. Additionally, the findings demonstrated, for the first time, that GCS and its products had a pro-survival role in cancer cells.

"This is exciting, because it has clinical impact," said Alexandra Straus, Ph.D., a postdoctoral fellow in the VCU Department of Cellular, Molecular and Genetic Medicine, who is also a collaborator on the paper. "As scientists that are at the bench, it's important to think about how a clinical trial might be working, and these findings can help us identify potential biomarkers for understanding which patients might benefit most."

Researchers in the lab of Can Senkal, Ph.D., interim director of the Lipidomics and Metabolomics Shared Resource and member of the Cancer Biology research program at Massey, treated cancer cell lines that represent primary focuses in Massey's catchment area—colon, ovarian and cervical cells—with eliglustat, a known inhibitor of GCS.

Eliglustat is typically used for the treatment of Gaucher disease type 1, a disease that occurs when a person has too little of the enzyme that breaks down glucosylceramide.

They found that eliglustat caused the cancer cells to die, not through ceramide accumulation as previously thought, but rather by decreasing glucosylceramide in the cells.

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