A man might take Viagra for erectile dysfunction and a statin for high cholesterol, treating two problems that seem to have nothing to do with cancer. But if he is later diagnosed with cancer, he may already be taking two medications linked to a lower risk of dying within five years.
In a study published in Cancer Research, researchers found that sildenafil, the active ingredient in Viagra, trapped cholesterol inside cancer cells and reduced lung metastases in several mouse models. Men who filled at least three sildenafil prescriptions before a cancer diagnosis had a 26 percent lower risk of death within five years. Among those who also used statins, the difference reached 32 percent.
“Our study underscores the importance of treating the whole patient – not just the cancer – when tailoring the most effective therapy,” said senior author Ayelet Erez in a press release.
How Viagra May Restrict Cancer Metastasis
Sildenafil’s familiar effect begins with an enzyme called PDE5A. The drug blocks it, causing a chemical signal called cGMP to rise. In the penis, that signal relaxes blood vessels and increases blood flow.
Erez and her colleagues found that cGMP may also bind to NPC1, a protein that carries cholesterol out of lysosomes, the cell’s recycling centers. When cGMP interfered with NPC1, less cholesterol could escape.
The cancer cells still contained cholesterol, but could not use it. This left them short of material needed to build and reshape their outer membranes. Spreading cancer cells require plenty of cholesterol to break away from a tumor, move through tissue, and invade another organ.
Without access to that supply, the cells had a harder time moving. The shortage also disrupted cell signaling and energy production.
The cancer cells tried to make up the difference by producing more cholesterol. This is where statins came in. Statins block cholesterol production, allowing the two drugs to cut off the supply in different ways. Sildenafil trapped stored cholesterol, while the statin prevented the cells from making more.
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Sildenafil Reduced Lung Metastases in Mice
The team tested sildenafil on mouse and human cancer cells from breast, lung, colon, and prostate cancers. Treated cells had more difficulty surviving and moving, although some responded more strongly than others.
The researchers then gave sildenafil to mice with breast, lung, or colon cancer. In all three models, the drug reduced the amount of cancer that spread to the lungs.
In the breast cancer model, sildenafil did little to slow the original tumor but significantly reduced the cancer in the lungs. The drug appeared to interfere more with the cancer’s ability to spread than with its growth at the original site.
The researchers saw similar results when they reduced the activity of PDE5A or NPC1. Giving the cells more cholesterol restored some of their ability to move.
Sildenafil generally worked better when paired with the statin lovastatin. The added effect was greater in the breast cancer model than in the colon cancer model, however, so the combination may not work equally well against every cancer.
Medical Records Showed a Survival Link
Using 20 years of health records, the researchers analyzed 40,567 male cancer patients ages 35 to 65. They compared five-year survival with sildenafil and statin prescriptions filled during the six months before diagnosis.
Men who filled at least three sildenafil prescriptions had a 26 percent lower risk of dying within five years. Among those who also used statins, the risk was 32 percent lower than among nonusers.
The analysis considered age, smoking, body mass index, socioeconomic status, other health conditions and cancer type. However, the records lacked information about cancer stage and treatment and could not prove that either medication improved survival. They also showed when a prescription was filled, not whether someone took it regularly.
Clinical trials are needed to learn whether the effect holds up in patients and which cancers, if any, respond. Until then, Viagra remains an erectile dysfunction drug, not a cancer treatment.
This article is not offering medical advice and should be used for informational purposes only.
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Article Sources
Our writers at Discovermagazine.com use peer-reviewed studies and high-quality sources for our articles, and our editors review for scientific accuracy and editorial standards. Review the sources used below for this article:
- This article references information from a study published in Cancer Research:PDE5a Inhibition Restricts Cancer Metastasis by Disrupting NPC1-Mediated Cholesterol Trafficking Through a Non-canonical cGMP-Dependent PathwayOpen Access