Researchers led by CSHL professor Lloyd Trotman’s lab have found that the pro-oxidant supplement menadione slows prostate cancer progression in mice. The supplement is a precursor to vitamin K, commonly found in leafy greens.
The findings are published in Science in an article titled, “Dietary pro-oxidant therapy by a vitamin K precursor targets PI 3-Kinase VPS34 function.”
In 2001, the National Cancer Institute’s SELECT trial sought to determine if an antioxidant vitamin E supplement could successfully treat or prevent prostate cancer. The trial involving 35,000 men was planned to last up to 12 years. However, after just three years, participants were told to stop taking their supplements. Not only had vitamin E failed to slow or prevent prostate cancer—more men taking the supplement started to get the disease. Seeing these results, Trotman thought, “If an antioxidant failed, maybe a pro-oxidant would work.”
“In light of emerging evidence that antioxidants can have cancer-promoting effects, Swamynathan et al., tested potential pro-oxidant interventions,” the researchers wrote. “In particular, the authors focused on menadione sodium bisulfite, a water-soluble precursor of vitamin K. As the authors anticipated, this menadione derivative suppressed prostate cancer growth.”
When mice with prostate cancer are given menadione, it interferes with the cancer’s survival processes. Trotman’s team discovered that menadione kills prostate cancer cells by depleting a lipid called PI(3)P, which works like an ID tag. Without it, the cells stop recycling incoming materials and eventually explode.
“It’s like a transport hub, like JFK. If everything that goes in is immediately de-identified, nobody knows where the airplanes should go next. New stuff keeps coming in, and the hub starts to swell. This ultimately leads to the cell bursting,” explained Trotman.
The researchers now hope to see the experiment translated to pilot studies in human prostate cancer patients.
“Our target group would be men who get biopsies and have an early form of the disease diagnosed,” Trotman said. “We wonder if they start to take the supplement, whether we would be able to slow that disease down.”
The discovery also shows that menadione may prove effective against myotubular myopathy. Trotman’s lab has found that depleting PI(3)P with menadione can double the lifespan of mice with this condition. The findings open a new door of understanding and may lead to new strategies and studies.
