A substance that comes from pine bark is a potential source for a new treatment of melanoma, researchers, including those of Indian-origin, have found.
Current melanoma drugs targeting single proteins can initially be effective, but resistance develops relatively quickly and the disease recurs.
In those instances, resistance usually develops when the cancer cell’s circuitry bypasses the protein that the drug acts on, or when the cell uses other pathways to avoid the point on which the drug acts.
“To a cancer cell, resistance is like a traffic problem in its circuitry,” said Gavin Robertson, professor of pharmacology, pathology, dermatology, and surgery and director of the Penn State Hershey Melanoma Center.
“Cancer cells see treatment with a single drug as a road closure and use a detour or other roads to bypass the closure,” he said.
Penn State researchers may have solved this problem by identifying a drug that simultaneously creates many road closures.
The researchers screened 480 natural compounds and identified leelamine, derived from the bark of pine trees, as a drug that can cause this major traffic jam in the cancer cell’s circuitry.
Leelamine could be the first of a new unique class of drugs that will simultaneously target several protein pathways, researchers said.
The study found that this drug shuts down multiple protein pathways, such as PI3K, MAPK and STAT3, at the same time in melanoma cells. These pathways are involved in the development of up to 70 per cent of melanomas.
Protein pathways like these help cancer cells multiply and spread, so shutting them down helps kill the cells.
“The cancer cell is addicted to these pathways. And when they are shut down, the bypass routes cannot be used. The result is the cancer cells die,” Robertson said.
Leelamine works by shutting down cholesterol transport and its movement around the cancer cell.
By shutting down cholesterol transport and movement, the exceptionally active survival communication that cancer cells require is shut down. The end result is death of the cancer cell.
Since normal cells are not addicted to the same high levels of activity in these pathways, the drug has a negligible effect on them.
The researchers demonstrated the results of this unique drug on cells growing in culture dishes and in tumours growing in mice. Leelamine inhibited tumour development in mice with no detectable side effects.
Other Penn State scientists who participated in the research are Raghavendra Gowda, research associate; SubbaRao V Madhunapantula, research associate; Omer F Kuzu, graduate student; and Arati Sharma, assistant professor of pharmacology.