Read time 3 minutes |
The Takeaway
CSHL Professor Lloyd Trotman and his team have discovered that menadione kills prostate cancer cells in mice by depleting a lipid known as PI(3)P. Their findings set the stage for pilot studies in human prostate cancer patients and point to a potential treatment target for myotubular myopathy, a rare and fatal disease diagnosed in infant boys.
Prostate cancer is a quiet killer. In most men, it’s treatable. However, in some cases, it resists all known therapies and turns extremely deadly. A new discovery at Cold Spring Harbor Laboratory (CSHL) points to a potentially groundbreaking solution. CSHL Professor Lloyd Trotman’s lab has 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 story begins more than two decades ago.
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.’ His new findings in mice show just that.
Trotman and his team monitored prostate cancer growth in mice treated with menadione (center), mice given menadione and an antioxidant (right), and an untreated control group (left). Press play to see what happened to the cancer cells in each group.
When mice with prostate cancer are given menadione, it messes with the cancer’s survival processes. Trotman’s team has 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. Trotman explains:
“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.”
This causes the cancer’s progression to slow significantly in mice. Trotman now hopes 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. We wonder if they start to take the supplement, whether we would be able to slow that disease down.”
Amazingly, Trotman’s research suggests menadione may also prove effective against myotubular myopathy, a rare condition that prevents muscle growth in infant boys. Those diagnosed rarely live beyond early childhood. Trotman’s lab has found that depleting PI(3)P with menadione can double the lifespan of mice with this condition.
If the results hold up in humans, it would mean that men with prostate cancer can enjoy a better quality of life and more time with their families. It could also mean more precious time for children born with an incurable disease.
Written by: Jen A. Miller | publicaffairs@cshl.edu | 516-367-8455
Funding
National Cancer Institute, Pershing Square Sohn Cancer Research Alliance, IC-MedTech, U.S. Department of Defense, Simons Foundation, AstraZeneca UK, Medical Research Council, Robertson Research Fund
Citation
Swamynathan, M.M., et al., “Dietary pro-oxidant therapy by a vitamin K precursor targets PI 3-Kinase VPS34 function”, Science, October 25, 2024. DOI: 10.1126/science.adk9167
Core Facilites
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“The Mass Spectrometry Core Facility provides state-of-the-art quantitative analysis of proteins and peptides, protein-protein interactions, and post-translational modifications. The resource also offers the ability to detect lipids, metabolites, and other small molecules. The facility supports experimental design, sample preparation, LC-MS analyses, and data analysis and interpretation.” — Director Paolo Cifani, Ph.D.
“The Microscopy Core Facility provides training, consultation, experimental design and technical assistance to investigators at CSHL in widefield, spinning disk laser scanning or point laser scanning confocal fluorescence microscopy, and super-resolution microscopy. In addition, the Microscopy Shared Resource provides customized state-of-the-art optical imaging and quantitative image analysis applications to support a wide range of scientific endeavors.” — Director Erika Wee, Ph.D.
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The Takeaway
CSHL Professor Lloyd Trotman and his team have discovered that menadione kills prostate cancer cells in mice by depleting a lipid known as PI(3)P. Their findings set the stage for pilot studies in human prostate cancer patients and point to a potential treatment target for myotubular myopathy, a rare and fatal disease diagnosed in infant boys.
Principal Investigator
Lloyd TrotmanProfessor
Cancer Center Deputy Director of Education
Ph.D., University of Zurich, 2001
Tags
cancer cancer treatment cellular communication in cancer core facilities genetic diseases Lloyd Trotman prostate cancer