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
Unlocking hidden soil microbes for new antibiotics
Most bacteria cannot be cultured in the lab-and that's been bad news for medicine. Many of our frontline antibiotics originated from microbes, yet as antibiotic resistance spreads and drug pipelines run dry, the soil [...]
By working together, cells can extend their senses beyond their direct environment
The story of the princess and the pea evokes an image of a highly sensitive young royal woman so refined, she can sense a pea under a stack of mattresses. When it comes to [...]
Overworked Brain Cells May Hold the Key to Parkinson’s
Scientists at Gladstone Institutes uncovered a surprising reason why dopamine-producing neurons, crucial for smooth body movements, die in Parkinson’s disease. In mice, when these neurons were kept overactive for weeks, they began to falter, [...]
Old tires find new life: Rubber particles strengthen superhydrophobic coatings against corrosion
Development of highly robust superhydrophobic anti-corrosion coating using recycled tire rubber particles. Superhydrophobic materials offer a strategy for developing marine anti-corrosion materials due to their low solid-liquid contact area and low surface energy. However, [...]
This implant could soon allow you to read minds
Mind reading: Long a science fiction fantasy, today an increasingly concrete scientific goal. Researchers at Stanford University have succeeded in decoding internal language in real time thanks to a brain implant and artificial intelligence. [...]
A New Weapon Against Cancer: Cold Plasma Destroys Hidden Tumor Cells
Cold plasma penetrates deep into tumors and attacks cancer cells. Short-lived molecules were identified as key drivers. Scientists at the Leibniz Institute for Plasma Science and Technology (INP), working with colleagues from Greifswald University Hospital and [...]
This Common Sleep Aid May Also Protect Your Brain From Alzheimer’s
Lemborexant and similar sleep medications show potential for treating tau-related disorders, including Alzheimer’s disease. New research from Washington University School of Medicine in St. Louis shows that a commonly used sleep medication can restore normal sleep patterns and [...]
Sugar-Coated Nanoparticles Boost Cancer Drug Efficacy
A team of researchers at the University of Mississippi has discovered that coating cancer treatment carrying nanoparticles in a sugar-like material increases their treatment efficacy. They reported their findings in Advanced Healthcare Materials. Over a tenth of breast [...]
Nanoparticle-Based Vaccine Shows Promise in Fighting Cancer
In a study published in OncoImmunology, researchers from the German Cancer Research Center and Heidelberg University have created a therapeutic vaccine that mobilizes the immune system to target cancer cells. The researchers demonstrated that virus peptides combined [...]
Quantitative imaging method reveals how cells rapidly sort and transport lipids
Lipids are difficult to detect with light microscopy. Using a new chemical labeling strategy, a Dresden-based team led by André Nadler at the Max Planck Institute of Molecular Cell Biology and Genetics (MPI-CBG) and [...]
Ancient DNA reveals cause of world’s first recorded pandemic
Scientists have confirmed that the Justinian Plague, the world’s first recorded pandemic, was caused by Yersinia pestis, the same bacterium behind the Black Death. Dating back some 1,500 years and long described in historical texts but [...]
“AI Is Not Intelligent at All” – Expert Warns of Worldwide Threat to Human Dignity
Opaque AI systems risk undermining human rights and dignity. Global cooperation is needed to ensure protection. The rise of artificial intelligence (AI) has changed how people interact, but it also poses a global risk to human [...]
Nanomotors: Where Are They Now?
First introduced in 2004, nanomotors have steadily advanced from a scientific curiosity to a practical technology with wide-ranging applications. This article explores the key developments, recent innovations, and major uses of nanomotors today. A [...]
Study Finds 95% of Tested Beers Contain Toxic “Forever Chemicals”
Researchers found PFAS in 95% of tested beers, with the highest levels linked to contaminated local water sources. Per- and polyfluoroalkyl substances (PFAS), better known as forever chemicals, are gaining notoriety for their ability [...]
Long COVID Symptoms Are Closer To A Stroke Or Parkinson’s Disease Than Fatigue
When most people get sick with COVID-19 today, they think of it as a brief illness, similar to a cold. However, for a large number of people, the illness doesn't end there. The World [...]
The world’s first AI Hospital, developed in China is transforming healthcare
Artificial Intelligence and its developments have had a revolutionary impact on society, and healthcare is not an exception. China has made massive strides in AI integrated healthcare, and continues to do so as AI [...]
