Menadione, a vitamin K precursor, shows promise in slowing prostate cancer in mice by disrupting cancer cell survival processes, with potential applications for human treatment and myotubular myopathy therapy.
Prostate cancer is a quiet killer. In most men, it’s treatable. While it’s treatable in many men, some cases prove resistant to all current therapies and become highly aggressive. Researchers at Cold Spring Harbor Laboratory (CSHL) have made a new discovery that could lead to a game-changing 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.
How Menadione Targets Cancer Cells
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.
“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,” explains Trotman.
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.
Reference: “Dietary pro-oxidant therapy by a vitamin K precursor targets PI 3-kinase VPS34 function” by Manojit M. Swamynathan, Shan Kuang, Kaitlin E. Watrud, Mary R. Doherty, Charlotte Gineste, Grinu Mathew, Grace Q. Gong, Hilary Cox, Eileen Cheng, David Reiss, Jude Kendall, Diya Ghosh, Colleen R. Reczek, Xiang Zhao, Tali Herzka, Saulė Špokaitė, Antoine N. Dessus, Seung Tea Kim, Olaf Klingbeil, Juan Liu, Dawid G. Nowak, Habeeb Alsudani, Tse-Luen Wee, Youngkyu Park, Francesca Minicozzi, Keith Rivera, Ana S. Almeida, Kenneth Chang, Ram P. Chakrabarty, John E. Wilkinson, Phyllis A. Gimotty, Sarah D. Diermeier, Mikala Egeblad, Christopher R. Vakoc, Jason W. Locasale, Navdeep S. Chandel, Tobias Janowitz, James B. Hicks, Michael Wigler, Darryl J. Pappin, Roger L. Williams, Paolo Cifani, David A. Tuveson, Jocelyn Laporte and Lloyd C. Trotman, 25 October 2024, Science.
DOI: 10.1126/science.adk9167
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
News
New technique overcomes technological barrier in 3D brain imaging
Scientists at the Swiss Light Source SLS have succeeded in mapping a piece of brain tissue in 3D at unprecedented resolution using X-rays, non-destructively. The breakthrough overcomes a long-standing technological barrier that had limited [...]
Scientists Uncover Hidden Blood Pattern in Long COVID
Researchers found persistent microclot and NET structures in Long COVID blood that may explain long-lasting symptoms. Researchers examining Long COVID have identified a structural connection between circulating microclots and neutrophil extracellular traps (NETs). The [...]
This Cellular Trick Helps Cancer Spread, but Could Also Stop It
Groups of normal cbiells can sense far into their surroundings, helping explain cancer cell migration. Understanding this ability could lead to new ways to limit tumor spread. The tale of the princess and the [...]
New mRNA therapy targets drug-resistant pneumonia
Bacteria that multiply on surfaces are a major headache in health care when they gain a foothold on, for example, implants or in catheters. Researchers at Chalmers University of Technology in Sweden have found [...]
Current Heart Health Guidelines Are Failing To Catch a Deadly Genetic Killer
New research reveals that standard screening misses most people with a common inherited cholesterol disorder. A Mayo Clinic study reports that current genetic screening guidelines overlook most people who have familial hypercholesterolemia, an inherited disorder that [...]
Scientists Identify the Evolutionary “Purpose” of Consciousness
Summary: Researchers at Ruhr University Bochum explore why consciousness evolved and why different species developed it in distinct ways. By comparing humans with birds, they show that complex awareness may arise through different neural architectures yet [...]
Novel mRNA therapy curbs antibiotic-resistant infections in preclinical lung models
Researchers at the Icahn School of Medicine at Mount Sinai and collaborators have reported early success with a novel mRNA-based therapy designed to combat antibiotic-resistant bacteria. The findings, published in Nature Biotechnology, show that in [...]
New skin-permeable polymer delivers insulin without needles
A breakthrough zwitterionic polymer slips through the skin’s toughest barriers, carrying insulin deep into tissue and normalizing blood sugar, offering patients a painless alternative to daily injections. A recent study published in the journal Nature examines [...]
Multifunctional Nanogels: A Breakthrough in Antibacterial Strategies
Antibiotic resistance is a growing concern - from human health to crop survival. A new study successfully uses nanogels to target and almost entirely inhibit the bacteria P. Aeruginosa. Recently published in Angewandte Chemie, the study [...]
Nanoflowers rejuvenate old and damaged human cells by replacing their mitochondria
Biomedical researchers at Texas A&M University may have discovered a way to stop or even reverse the decline of cellular energy production—a finding that could have revolutionary effects across medicine. Dr. Akhilesh K. Gaharwar [...]
The Stunning New Push to Protect the Invisible 99% of Life
Scientists worldwide have joined forces to build the first-ever roadmap for conserving Earth’s vast invisible majority—microbes. Their new IUCN Specialist Group reframes conservation by elevating microbial life to the same urgency as plants and [...]
Scientists Find a Way to Help the Brain Clear Alzheimer’s Plaques Naturally
Scientists have discovered that the brain may have a built-in way to fight Alzheimer’s. By activating a protein called Sox9, researchers were able to switch on star-shaped brain cells known as astrocytes and turn them into [...]
Vision can be rebooted in adults with amblyopia, study suggests
Temporarily anesthetizing the retina briefly reverts the activity of the visual system to that observed in early development and enables growth of responses to the amblyopic eye, new research shows. In the common vision [...]
Ultrasound-activated Nanoparticles Kill Liver Cancer and Activate Immune System
A new ultrasound-guided nanotherapy wipes out liver tumors while training the immune system to keep them from coming back. The study, published in Nano Today, introduces a biodegradable nanoparticle system that combines sonodynamic therapy and cell [...]
Magnetic nanoparticles that successfully navigate complex blood vessels may be ready for clinical trials
Every year, 12 million people worldwide suffer a stroke; many die or are permanently impaired. Currently, drugs are administered to dissolve the thrombus that blocks the blood vessel. These drugs spread throughout the entire [...]
Reviving Exhausted T Cells Sparks Powerful Cancer Tumor Elimination
Scientists have discovered how tumors secretly drain the energy from T cells—the immune system’s main cancer fighters—and how blocking that process can bring them back to life. The team found that cancer cells use [...]
