Statins, prostate cancer and mitochondria

In honor of Fathers’ Day, we are examining a connection between two older-male-centric topics: statins and prostate cancer.

Statins are a very widely prescribed class of drugs used to lower cholesterol levels, for the purpose of preventing cardiovascular disease. In cell culture, they appear to kill prostate cancer cells, but the epidemiological evidence is murkier. Statin effects on prostate cancer incidence have been up in the air, but recent reports point to the possibility that starting statins may slow progression, after a man has been diagnosed with prostate cancer.

Winship Cancer Institute researchers have some new results that shed some light on this effect. John Petros, Rebecca Arnold and Qian Sun have found that mutations in mitochondrial DNA make prostate cancer cells resistant to cell death induced by simvastatin [Zocor, the most potent generic statin]. Sun recently presented the results at the American Urological Association meeting in Orlando.

In other forms of cancer such as breast and lung cancer, genomic profiling can determine what DNA mutations are driving cancer growth and what drugs are likely to be effective in fighting the cancer. The prostate cancer field has not reached the same point, partly because prostate cancers are not generally treated with chemotherapy until late in the game, Petros says. But potentially, information on mitochondrial mutations could guide decisions on whether to initiate statin (or another) therapy.

“This is part of our soapbox,” he says. “When we are looking at mutational effects on prostate cancer, let’s be sure to include the mitochondrial genome.”

Winship’s Carlos Moreno and his colleagues are working on the related question of biomarkers that predict prostate cancer progression, after prostatectomy surgery and potentially after just a biopsy.

Petros had previously found in a collaboration with Douglas Wallace that mutations in the mitochondrial cytochrome c oxidase gene both enhance prostate cancer growth and are more common in prostate cancers than healthy tissue. More recently, his team has been looking at potential mechanisms and the effects of common drugs — they didn’t start out looking at statins specifically.

“We screened antioxidants, NSAIDs like aspirin, resveratrol, all sorts of things. Most of these made no difference but we saw a huge difference with simvastatin,” Petros says.

Mitochondria are well-known for being cells’ power plants. They’re critical infrastructure — if they are damaged or their function is interfered with, then cells have triggers to undergo apoptosis or programmed cell death.

In Sun’s presentation, the mutation in question [T6124C in the cytochrome c oxidase gene] impairs mitochondrial function and increases the generation of reactive oxygen species. How more reactive oxygen makes a cancer cell more hardy may have to do with the Warburg effect – a phenomenon by which cancer cells tune down their mitochondria to enhance their growth. Researchers elsewhere have found ROS-enhancing mitochondrial mutations that enhance tumor growth and metastasis in other forms of cancer.

The statin-mitochondria connection was unexpected, although there were some hints in that a common side effect of statins — muscle pain – is also thought to have to do with mitochondria. What’s next? Arnold says their research is still at an early stage, and they need to test more mutations and more patient-derived cell lines.

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Posted on by Quinn Eastman in Cancer Leave a comment

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Quinn Eastman

Science Writer, Research Communications qeastma@emory.edu 404-727-7829 Office

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