Everyone’s favorite blue little pill might be even more impressive than we knew. A recent study suggests that sildenafil, the active ingredient in the erectile dysfunction drug Viagra, may actually have a potent anti-cancer effect as well.
Researchers in Israel studied how sildenafil affected cancer cells in the lab, and found that it appears to help prevent cancers from spreading further by inhibiting the cells’ ability to use cholesterol. The findings could someday point to a novel means of tackling metastatic cancers, the researchers say.
“We have uncovered a new biological pathway that links a well-known signaling molecule to cholesterol regulation within cells, and shown how this pathway can be harnessed to interfere with the ability of cancer cells to form metastases,” said senior study author Ayelet Erez, a cancer researcher at the Weizmann Institute of Science, in a statement from the university.
Sildenafil and cancer
By their very nature, cancer cells are different in many ways from their normal counterparts. One such example is how they might rely on less commonly used chemical chain reactions to help them keep growing and to spread elsewhere in the body (a process called metastasis). The researchers were particularly interested in understanding how cancer cells use cholesterol to fuel this unchecked growth, and whether this process could be safely interrupted.
Sildenafil primarily affects the body by inhibiting the enzyme phosphodiesterase type 5 (PDE5), which then blocks the breakdown of another molecule called cGMP. Higher circulating cGMP levels allows certain blood vessels to stay dilated for longer, particularly those in the penis, thus helping treat erectile dysfunction. The researchers discovered that cGMP can also bind to a protein that helps transport cholesterol within cells, meaning that higher cGMP levels can reduce cholesterol transport. And as it turns out, cancer cells might be especially vulnerable to this disruption.
The researchers studied the effects of sildenafil on mouse and human cancer cells in the lab. The drug appeared to slow cholesterol transport within these cancer cells, they found, which made them less able to metastasize. They then studied the medical records of five million patients within Clalit Health Services, Israel’s largest public provider of healthcare. People with cancer also taking sildenafil appeared to survive longer than similar patients not taking sildenafil, they found.
The team’s results were published last week in the journal Cancer Research.
A hidden weapon?
This research alone doesn’t prove that sildenafil and similar drugs can be cancer-busters. More studies will be needed to verify the findings and quantify whether any effect is clinically meaningful. Many drugs can seemingly work against cancer cells in a petri dish but end up providing no actual survival benefit in real life cancer patients.
Still, the researchers believe they’ve discovered a new method of weakening cancers via their added reliance on this pathway of transporting cholesterol—one that other drugs beside sildenafil could possibly exploit. When the researchers combined sildenafil with statins, a class of cholesterol-lowering drugs, it further limited cancer metastasis, for instance. Likewise, cancer patients who took both drugs were even less likely to die of cancer in their analysis of medical records.
“Together, these findings identify increasing cGMP levels through PDE5a inhibition as a potential strategy to restrict metastasis and offer a potential mechanistic basis for the beneficial effects of sildenafil,” the researchers wrote.
If sildenafil does eventually end up having another life as a cancer treatment, it might not be the first unexpected use of this drug. Studies have also suggested PDE5 inhibitors can potentially treat dementia, too.
