Cholesterol-Fighting Statins Show Potential As Cancer Treatment


Millions of Americans take statins as a prescription drug to lower their cholesterol levels. Ongoing research, however, indicates that their benefits might extend even further to cancer treatment by suppressing tumor growth at a molecular level.

Statins' Potential Tumor-Suppressing Properties

Known under names such as Lipitor (atorvastatin), Pravachol (pravastatin), and Mevacor (lovastatin), statins are widely used to successfully keep cholesterol levels under control and hence prevent cardiovascular disease, with years of research to back up their safety and good tolerance by patients.

According to ongoing observation carried out by Prof. Tomoo Iwakuma and his team in the Department of Cancer Biology at the University of Kansas, statins may also have the potential to prevent the development of cancers by degrading mutant versions of the protein p53 (mutp53).

In its normal state, p53 plays a crucial role as a tumor suppressant by keeping body cells from dividing and growing too quickly. When it becomes mutated, however, cell division is no longer properly controlled, hence resulting in abnormal rapid growths that turn into tumors.

The team also investigated the behavior of heat shock proteins that are responsible for correcting misfolded proteins, specifically DNAJA1, which binds to the mutated p53 and inhibits the action of an enzyme that flags abnormal or damaged proteins for destruction. Statins may thus prevent mutant p53 from binding with DNAJA1 and in turn help it bind with the enzyme that triggers its degradation and hence prevent tumor growth.

Cancer Protein Research

The study began four years ago, when the team worked together with the High Throughput Screening Lab on the University of Kansas Lawrence to find compounds that would successfully degrade mutant p53. Almost 9,000 were tested, out of which only 2,400 were FDA-approved. Out of the 10 compounds that showed promising p53-degrading properties in the screenings, some of them were statins, scientists discovered.

In order to rule out false positives, the team had to verify the results first in cells and then in mice. They injected the mice with cells containing mutp53 and, after the tumors formed, treated the mice with high doses of statins for 21 days.

As opposed to the controls, the tumors did not develop in the mice that were treated with statins. The researchers also concluded that statins only worked on structurally mutated p53 and not on p53 mutated at the spot where it binds to DNA. This led the study one step further, as the research, up to that point, had not considered the type of mutation undergone by p53.

This, however, is only the beginning of very promising research. While findings so far suggest that statins' effects on mutated p53 may exhibit great efficacy in cancer therapy, scientists have many challenges ahead. Potential challenges, for example, reside in ways to target DNAJA1 directly, since its absence results in the degradation of mutp53.

Mutations of this protein make human cancer cells more metastatic. Therefore, scientists need to focus on proper mechanisms for its degradation, which, in combination with chemotherapy, might prove to be a more effective approach to treating cancer.

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