Statins potential agent in cancer treatment
Devreotes and his team intend to perform further research on the effects of statins in people with cancer and compounds that block GGPP.
Researchers looked at a group of 2,500 drugs already approved by the US Food and Drug Administration (FDA) to determine which ones had the best kill rate of genetically engineered mutant cells. These cells carry a mutation in the PTEN gene: this gene is responsible as a tumour suppressor, thus mutations in this gene are a step in the development of some cancers. [Med Sci Monit 2004;10(10):RA235–241]
According to one of the study authors, Peter N. Devreotes, Ph.D, professor of cell biology at Johns Hopkins University School of Medicine, there already exists epidemiological indications that people who take statins over the long term have fewer and less aggressive cancers, and statins can kill cancer cells in the laboratory. Among the 2,500 drugs tested, statins (in particular pitavastatin), emerged as a top contender in cancer-killing ability. Most of the other drugs had no effect or were lethal similarly to both normal and engineered cells. [Proc Natl Acad Sci U S A. 2020;117(8):4158–4168]
Statins block the production of the molecule geranylgeranyl pyrophosphate, or GGPP, which is responsible for connecting cellular proteins to cellular membranes. When pitavastatin and GGPP were added to human cancer cells with PTEN mutations, GGPP prevented the statin from killing those cells, thus leading to the conclusion that GGPP may be an important molecule in cancer cell survival.
The researchers then looked at cancer cells engineered to lack the enzyme which manufactures GGPP and discovered that these cells were not moving. Normally, cancer cells move vigorously, consuming vast amounts of nutrients to fuel their growth. Devreotes’ team postulated that the cells were starving to death due to the inability to absorb nutrients from their environment.
To test this hypothesis, they measured statin-treated cells’ nutrient intake by adding a fluorescent tag to proteins in the cells’ environment. They observed that normal human cells, even though treated with statins, glowed due to ingestion of the fluorescent tag. Conversely, human cancer cells with PTEN mutations and treated with statins had almost no glowing proteins in their cells, thus confirming the idea that these cells were being starved by the addition of statins.