Cholesterol inhibitors block proliferation of medulloblastoma cells

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Cholesterol and specific oxysterols are needed for signal transduction in medulloblastoma cells. Blocking their synthesis can halt proliferation of the malignant cells, a new in vitro study shows.

Previous reports have suggested that errors in Sonic hedgehog (Shh) signal transduction play a key role in the formation of medulloblastoma and other tumors. Sterol synthesis is needed for such transduction to occur, but it has been which specific products are required.

As reported in the May 15th early edition of the Proceedings of the National Academy of Sciences, Dr. Matthew P. Scott and Dr. Ryan B. Corcoran, from Stanford University School of Medicine in California, found that cholesterol or specific oxysterols are, in fact, the products needed for Shh signal transduction in medulloblastoma cells.

Blocking sterol synthesis reduced Shh target gene transcription and stopped Shh pathway-dependent proliferation, the report indicates. Treatment with exogenous cholesterol or specific oxysterol overcame these effects.

Further analysis suggested that the oxysterols affected the Shh pathway by regulating a related compound called the Smoothened protein.

"Inhibition of Shh signaling by sterol synthesis inhibitors may offer a novel approach to the treatment of medulloblastoma and other Shh pathway-dependent human tumors," the authors conclude.