The study by Johns Hopkins Kimmel Cancer Center found that the pairing of cholesterol-lowering lovastatin and cyclopamine killed 63% of medulloblastoma cells. By contrast, using either agent alone wiped out fewer than 20% of cells.
However, the researchers caution that the cyclopamine-lovastatin combination has yet to be tested in animals but they conclude that the tumor cell-killing by this therapy is encouraging.
Cyclopamine works by blocking the so-called “hedgehog” pathway, known to promote and guide cell and organ growth. The investigators believe that blocking hedgehog with cyclopamine makes cancer cells more susceptible to lovastatin. Along with its cholesterol effects, lovastatin is known to cause cancer cells to self-destruct through a process called apoptosis.
“We already knew from earlier research that hedgehog controls brain cell survival and growth, and that blocking signals in this pathway may stop uncontrolled growth of cancer cells,” said Charles Eberhart, associate professor of pathology, ophthalmology and oncology at Johns Hopkins Kimmel Cancer Center.
“But the new work shows the hedgehog blockade may halt another powerful cell-survival signal, and lovastatin could provide the added boost necessary to kill more cancer cells.”
Specifically, the scientists found links between the expression of key hedgehog-related genes in medulloblastoma cells and another cell signal already tied to cancer, Bcl-2. The team believed that combination of a hedgehog blockade and a pro-apoptosis drug like lovastatin would kill more cancer cells.
When researchers noticed that Bcl-2 and hedgehog expression increased in tandem in medulloblastoma cells, they tried adding hedgehog-blocking cyclopamine to the cells and found that Bcl-2 production dwindled and tumor cells died off.