Viagra's active ingredient may have a surprising role beyond treating erectile dysfunction, with new research suggesting it could interfere with the biological processes that allow cancer cells to spread to other parts of the body.
The study by scientists at the Weizmann Institute of Science found that sildenafil may restrict cancer metastasis by disrupting how cancer cells access and use cholesterol. The findings raise the possibility that an existing drug could eventually be repurposed as part of strategies aimed at preventing cancer from spreading, although the research is still far from proving that Viagra can treat cancer in people.
A Drug Best Known for Erectile Dysfunction Takes a New Turn
Sildenafil was originally developed to treat cardiovascular conditions before becoming widely known as Viagra, a medication used to treat erectile dysfunction. Researchers are now investigating whether its effects on a cellular signaling pathway could have implications for cancer biology.
The research team found that sildenafil blocks an enzyme called phosphodiesterase type 5 (PDE5). This increases levels of a signaling molecule known as cyclic guanosine monophosphate, or cGMP.
While cGMP is best known for helping relax blood vessels, the researchers found that it may also affect the movement of cholesterol inside cells. Elevated cGMP appeared to interfere with NPC1, a protein involved in transporting cholesterol out of cellular compartments called lysosomes.
That disruption left less cholesterol available for cancer cells to use.
Cholesterol Matters When Cancer Spreads
Cancer cells need to adapt quickly as they move away from a primary tumor. Cholesterol is an important component of cell membranes and supports cellular processes that enable cancer cells to migrate and invade distant organs.
In the study, disrupting cholesterol trafficking appeared to impair cancer cells' ability to move and form metastases. The researchers reported that sildenafil caused cholesterol to accumulate inside lysosomes, reducing the amount available elsewhere in the cell.
The effect appeared particularly significant in cancer cells, which the researchers said were more vulnerable to disrupted cholesterol availability because of differences in their lysosomal gene expression.
The experiments included cancer cell cultures derived from human patients as well as multiple mouse models, providing evidence across laboratory and animal settings. However, these findings do not establish that sildenafil can prevent or treat metastatic cancer in humans.
Viagra and Statins May Have a Combined Effect
The researchers also explored whether sildenafil could work alongside statins, a widely prescribed class of cholesterol-lowering medications.
The combination appeared to produce an additive effect in limiting cancer's ability to spread. While sildenafil interfered with the movement of cholesterol within cells, statins reduced the body's ability to produce new cholesterol, potentially targeting cancer cells' cholesterol supply through two distinct mechanisms.
The researchers also analyzed health records from approximately 5 million members of Israel's Clalit Health Services. Their statistical analysis found that cancer patients who used sildenafil had significantly improved survival, with an additional benefit observed among those who also took statins.
However, the observational nature of the health-record analysis means it cannot establish that sildenafil caused the improved survival. Other differences between patients who did and did not take the medication could have influenced the results.
Not Quite a Cancer Treatment
The study adds to growing interest in drug repurposing, in which existing medications are investigated for potential uses beyond their original purpose. Because sildenafil has already been widely used, researchers have access to extensive information about its safety and biological effects.
Still, experts caution that promising laboratory findings do not automatically translate into effective cancer treatments. The new research involved cell and animal experiments, alongside observational human data, rather than randomized clinical trials designed to determine whether sildenafil can prevent metastasis or extend survival.
For now, the findings point to a potential new avenue for cancer research rather than a reason for patients to take Viagra as a cancer treatment.
The researchers said their work highlights how cancer progression may depend not only on genetic changes within tumors but also on the body's metabolic environment and medications a patient may already be taking.
Further clinical research will be needed to determine whether targeting cholesterol trafficking with PDE5 inhibitors such as sildenafil, alone or alongside statins, can safely and effectively prevent cancer from spreading in people.
