Amino acid deprivation proves deadly to skin cancer cells

Amino acids are the building blocks of protein and are critical for muscle production. They are also critical for the survival of cancer cells, including those in melanoma, the deadliest form of skin cancer.

The lab of Whitehead Institute Member David Sabatini has discovered that when the melanoma cells are deprived of the amino acid leucine, they die, suggesting a possible strategy for therapeutic intervention.

When normal cells lack sufficient levels of amino acids, they activate a process known as autophagy. Much like a starved body breaking down muscle for nutrients, autophagy causes a cell to break down its own protein-based structure to its amino acid components. However, melanoma cells deprived of leucine fail to detect its absence, which means autophagy never kicks in, and the cells eventually die.

Leucine deprivation in melanoma cells

© Cancer Cell, 2011. In the above images of melanoma cells, autophagy is indicated by the absence of green markers. Left: Control-state melanoma cells. Center: Melanoma cells deprived of all essential amino acids (autophagy is activated). Right: Melanoma cells deprived of leucine (autophagy fails to activate).

To explore leucine deprivation as a potential approach for cancer therapy, Joon-Ho Sheen, a postdoctoral researcher in the Sabatini lab, tested a mouse with melanoma tumors. By eliminating leucine from the mouse’s diet (leucine is one of nine “essential” amino acids that the body must ingest), and introducing a drug that inhibits autophagy, Sheen was able to kill the melanoma cells and significantly reduce the tumor size.

Though the initial results are promising, further research is needed to investigate leucine deprivation in humans and to find more efficient methods of targeting autophagy in melanoma cells.

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