- A new study suggests a tightly targeted and effective way of killing prostate cancer cells.
- The method involves a precursor of vitamin K that uses a pro-oxidant reaction to rob the cells of a lipid they require to manage cell waste successfully, causing them to overload and explode.
- The same treatment also appears to provide hope for treating a debilitating genetic muscle disease called ‘X-linked myotubular myopathy.‘
A pro-oxidant supplement may offer a uniquely effective means of targeting and killing prostate cancer cells, according to a new study in mice conducted at Cold Springs Harbor Laboratory (CSHL) in Cold Spring, NY.
The authors of the study — which appears in Science — found that the supplement, menadione, a precursor of vitamin K, significantly suppressed cancer growth in mice and in more than 100 human cells and mouse cancer cells in the laboratory.
It appears menadione inhibits a lipid, phosphatidylinositol 3-phosphate (PI(3)P), that allows cells to identify, sort, and correctly process incoming materials. Unable to do so, the cancer cells become overwhelmed, causing them to explode and die.
“It’s like a transport hub, like JFK [airport],“ study author Lloyd Trotman, PhD, professor and Cancer Center Deputy Director of Education at CSHL, noted in a press release. “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 prostate cancer cell death provides a more definitive resolution of the disease than current treatments, such as radiation, that force prostate cancer into dormancy, from which it may at some point develop resistance.
The researchers also discovered that a relative excess of PI(3)P is a cause of a fatal genetic muscle disease, X-linked myotubular myopathy.
Menadione administration in mice bred with X-linked myotubular myopathy suggested menadione should be further investigated as a treatment for this disease.
Molecules that cause oxidation in the body are called oxidants. Oxidation reactions in the body can lead to free radicals, which are made during many processes, including inflammation, stress, and aging.
Oxidants serve valuable roles such as disposing of no longer needed cells and germs, and can help fight pathogens. Oxidants are kept in check by antioxidants the body produces.
When there are too many oxidants relative to antioxidants, oxidative stress occurs, and damage to Healthy cells may result, leading to cancers and various chronic diseases.
During aging, the body makes fewer antioxidants. Fortunately, antioxidants are available in many foods and in supplements.
A large study investigating the potential of antioxidant treatment of prostate cancer, the
The trial was halted three years into the planned 12-year study period when it was observed that antioxidant intake was associated with an increase in prostate cancer rather than a reduction, and participants were instructed to cease taking the antioxidants.
“Despite the initial failure of selenium and vitamin E, oxidation remains an active area of investigation,” oncologist and hematologist Daniel Landau, MD, medical director of virtual hematology at the Medical University of South Carolina in Charleston, who was not involved in the recent study, told Medical News Today.
The authors of the new study decided to explore the other side of the oxidation coin: What about pro-oxidants? They devised the new trials using menadione in which the vitamin K precursor would provide a pro-oxidant effect.
“One of the concerns with therapies that affect oxidation is that some cells do better with antioxidation and some with pro-oxidation,” Landau pointed out. “Therefore, selective targeting of cancer cells is important.”
“This is not yet something that we are able to do with most systemic therapies. However, antibody drug conjugates do exist, which can control which cells are targeted. Perhaps that is why earlier oxidation studies failed,” he suggested. “We couldn’t selectively target the cells of interest.”
With menadione, this problem may be solved due to the nature of prostate cancer cells’ natural deficiency of PI(3)P.
While healthy cells have enough of this lipid to overcome the inhibitory effect of menadione, prostate cancer cells do not, and thus are more grievously impacted by its reduction.
Furthermore, Trotman told MNT that when prostate cancer cells burst, there is no risk of cancer spreading “since any bursting of a cell is a terminal death event; there is no expectation of metastasis.”
“Metastasis requires very fit cells that migrate out of tissues intact,” he explained.
Side effects of menadione are not a concern, according to Trotman, who noted that:
“It was developed as a trigger for vitamin K production since it is the immediate precursor of that vitamin. Vitamin K is essential for blood clotting.”
“Side effects are hardly seen when administered orally. It is often used in animal feed as a source for vitamin K,” he also added.
As for “side effects of tissue damage“, these only occur “upon high dose injections into animals,“ Trotman noted. “Our study only uses oral menadione delivery.”
“While it is true that most prostate cancers are slow-growing cancers, we often fall short on options for patients with advanced disease who are expected to live for a long period of time,” Landau admitted.
Explaining who might benefit the most from supplementation with menadione, Trotman said that: “We would see this primarily for patients who are under surveillance for progression of prostate cancer.
“Patient surveillance is either watchful waiting (minimal invasive testing) or active surveillance (repeated diagnostic testing),” he noted.
“In prostate cancer this would be a diagnosis of Gleason Grade 7, which is a grey zone between indolent (Gleason 6- left alone) and aggressive (Gleason 8-10, intervention needed),” Trotman explained.
“[W]hile at this time, oxidation is not a practical approach to care, we do require newer and novel therapies. Especially ones with low side effect profiles,” Landau said. “There is hope from studies like this one that a new option may be on the horizon.”
