Statins: How the drug prevents heart attacks and strokes

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The team at John Hopkins Medicine investigated the biological effects of more than 2,500 medications on human cells studied under a microscope. The focus was on a cancer gene, called PTEN, which led to the surprising discovery. Dr Peter Devreotes said: “There have been epidemiological indications that people who take statins long term have fewer and less aggressive cancers, and that statins can kill cancer cells in the laboratory. “But our research was not initially designed to investigate possible biological causes of these observations.”

The PTENA gene codes for an enzyme that suppresses tumour growth, but for the study, a mutation in the cell was genetically engineered.

Among the thousands of drugs tests, statins – and in particular, pitavastatin – had the best “cancer-killing ability”.

Other medications had no effect at all, or killed normal and engineered cells at the same rate.

Equal concentrations of pitavastatin caused cell death in nearly all of the engineered cells, but very few in normal cells.

Investigating further, the research team observed the molecular pathways that statins are likely to affect.

Statins are well known to block a liver enzyme that makes cholesterol, but the drug also blocks the creation of geranylgeranyl pyrophosphate (GGPP).

GGPP is responsible for connecting cellular proteins to cellular membranes.

Interestingly, when pitavastatin and GGPP were added to human cancer cells with the PTEN mutations, GGPP prevented statins from killing cancer cells.

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This suggests that GGPP might be a key molecule to cancer cell survival in humans.

Gaining momentum, the next step involved looked at cells engineered to lack the enzyme that makes GGPP.

Cancer cells are usually “a bundle of moving energy”, sucking up nutrients around them to maintain their unchecked growth.

However, in the experiment where GGPP was removed, cancer cells stopped moving.

Suspecting the cancer cells were “starving to death”, Dr Devreotes furthered his experiment.

Tagging proteins with fluorescent markers, normal human cells glowed brightly as they ingested protein from their surroundings, regardless if statins were added into the mix.

However, human cells with PTEN mutations “took in almost no glowing proteins after the scientists added statins”.

The inability of statin-treated cancer cells to take in proteins is what effectively led to their starvation.

Dr Devreotes and his team have plans for further research on this illuminating area of research.

They want to investigate the effects of statins in people with cancer and compounds that block GGPP.

The results appeared in the Proceedings of the National Academy of Sciences journal.

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