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Statins Can Be Future Cancer Treatments, Study Shows

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Researchers from the University of Kansas Medical Center have found that high doses of medicinal drugs called statins mainly used to battle high cholesterol can ruin a rogue protein produced through a broken gene that is related to nearly half of all human cancers.

Tomoo Iwakuma, M.D., Ph.D., an associate professor in the Department of Cancer Biology and his group have published the primary study showing how the use of statins, such as Lipitor (atorvastatin), Crestor (rosuvastatin) and Mevacor (lovastatin), can shut down structurally mutated p53 proteins that may accelerate cancer progression, while not harming proteins produced by healthy p53 genes. Even though statins are not a cancer cure per se, the figuring out of how they have an effect on mutated varieties of p53 would result in new medicinal drugs designed peculiarly to knock out the damaged p53.

P53 Gene And Cancer

Cancer is caused by mutations to the genes that keep watch over cell growth or cell loss of life. Of the thousands of genetic culprits which were implicated with various cancers, p53, dubbed the “guardian of the genome,” is the mightiest of them all. Mutant types of p53 had been located in nearly half of all malignant tumors and practically every form of human cancer.

When p53 works adequately, it produces proteins that keep cells from developing and dividing too fast. When p53 becomes mutated, either spontaneously or via heredity, its regulating functions do not work and cells can grow out of control, forming tumors and invading tissues — that’s cancer.

Compounding the quandary that mutant p53 can no longer suppress the growth of tumors is that indisputable fact that it may also in reality accelerate the development of cancer and drug resistance.

The project for Iwakuma and his group was to find out methods to eliminate the misbehaving protein, at the same time leaving cells containing healthful p53 wanted for average cell growth unharmed.

Four years ago, Iwakuma and his lab group collaborated with the High Throughput Screening Laboratory (HTC) on the University of Kansas Lawrence campus to screen compounds to find out which of them would degrade mutant p53. Of the 9,000 compounds they tested, about 2,400 had been FDA-authorized medicinal drugs, while the others had been non-FDA permitted and uncharacterized compounds.

When Iwakuma acquired an email from the HTC listing down the 10 compounds that the screenings had proven promise in reducing mutant p53 levels, he was bowled over to look that some of them were statins.

Early screenings most likely produce false positives, so Iwakuma had to verify the lab results, first trying them in cells and then in mice. The KU researchers injected the mice with cells expressing mutant p53, waited for tumors to develop, and then treated them with excessive doses of statins for 21 days. They discovered that tumors didn’t develop well in mice dealt with statins compared to the controls, and they learned the statins worked simplest on structurally mutated (misfolded) p53, versus p53 mutated on the spot where it binds to DNA. This was an important discovery, in particular since medical research with statins had not viewed this kind of p53 mutation.

It was found out that the equal mechanisms that help statins lower cholesterol are at work preventing mutant p53 from binding to DNAJA1, leaving these mutant proteins unprotected. As a result, mutant p53 is free to connect to the enzyme that brings about its degradation. And on account that mutant p53 isn’t always present in ordinary cells, all this occurs without affecting healthy cells.

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