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New method monitors early sign of oxidative stress in cancer
September 14, 2009ANN ARBOR, Mich.-The growth of cancerous tumors is fueled, at least in part, by the buildup of free radicals-highly reactive oxygen-containing molecules.
It stands to reason, then, that cancer should respond to treatment with antioxidants, which inhibit the rogue radicals, or with pro-oxidants, which go the opposite direction, increasing "oxidative stress" on cancer cells to the point of vanquishing them.
But experiments with such treatments have had mixed results, possibly because patients differ in their "redox profiles," or oxidative stress levels. Being able to monitor a marker of oxidative stress that is associated with the activation of tumor cell growth pathways, particularly at an early stage, and then tailor treatments accordingly would allow for more targeted studies and might improve the odds of success with antioxidants and pro-oxidants, said University of Michigan chemical biologist Kate Carroll.
A new method developed by Carroll and postdoctoral research fellow Young Ho Seo makes such monitoring possible and reveals that different individuals and even different tumor types have different redox profiles. The method and the research behind it are described in a paper scheduled for online publication in the Proceedings of the National Academy of Sciences during the week of Sept. 7.
The new method detects sulfenic acid in proteins-a tipoff to early oxidative stress and to a specific protein modification associated with cell growth pathways. Sulfenic acid is produced when a particular oxidant, hydrogen peroxide, reacts with the protein building block cysteine. But because the chemical modification involved is so small and transient, it has been difficult to detect. To get around that problem, Carroll and Seo used a chemical probe that "traps" sulfenic acid and tags it for recognition by an antibody. The antibody is labeled with a fluorescent dye that glows when observed with a fluorescence microscope.
The researchers then used the method to assess sulfenic acid levels as a marker of oxidative stress in several systems, including a panel of breast cancer cell lines.
"For each line, we saw a very distinct pattern of sulfenic acid modifications," indicating different oxidative stress levels and hinting at differences in the underlying molecular events associated with tumor growth," said Carroll, assistant professor of chemistry and a research assistant professor in the Life Sciences Institute. "Whether the patterns we see will correlate with response to antioxidant treatment or other therapies that modulate oxidative stress level remains to be seen, but now we at least have a way to investigate that question."
Next, Carroll's group wants to determine which specific proteins in the cell are being modified and what roles, if any, those proteins play in the disease process. "Some of the modified proteins may not play any role, but I'm sure it will turn out that many of them do," Carroll said. "Once we find out which proteins are involved, we can target them directly rather than using global treatments like antioxidants."
The U-M Office of Technology Transfer is working on commercialization of the technology. Patent protection has been applied for, and the compounds used in this research soon will be commercially available.
The researchers received funding from the Life Sciences Institute, the Leukemia & Lymphoma Society and the American Heart Association.
University of Michigan
A new method developed by Carroll and postdoctoral research fellow Young Ho Seo makes such monitoring possible and reveals that different individuals and even different tumor types have different redox profiles. The method and the research behind it are described in a paper scheduled for online publication in the Proceedings of the National Academy of Sciences during the week of Sept. 7.
The new method detects sulfenic acid in proteins-a tipoff to early oxidative stress and to a specific protein modification associated with cell growth pathways. Sulfenic acid is produced when a particular oxidant, hydrogen peroxide, reacts with the protein building block cysteine. But because the chemical modification involved is so small and transient, it has been difficult to detect. To get around that problem, Carroll and Seo used a chemical probe that "traps" sulfenic acid and tags it for recognition by an antibody. The antibody is labeled with a fluorescent dye that glows when observed with a fluorescence microscope.
The researchers then used the method to assess sulfenic acid levels as a marker of oxidative stress in several systems, including a panel of breast cancer cell lines.
"For each line, we saw a very distinct pattern of sulfenic acid modifications," indicating different oxidative stress levels and hinting at differences in the underlying molecular events associated with tumor growth," said Carroll, assistant professor of chemistry and a research assistant professor in the Life Sciences Institute. "Whether the patterns we see will correlate with response to antioxidant treatment or other therapies that modulate oxidative stress level remains to be seen, but now we at least have a way to investigate that question."
Next, Carroll's group wants to determine which specific proteins in the cell are being modified and what roles, if any, those proteins play in the disease process. "Some of the modified proteins may not play any role, but I'm sure it will turn out that many of them do," Carroll said. "Once we find out which proteins are involved, we can target them directly rather than using global treatments like antioxidants."
The U-M Office of Technology Transfer is working on commercialization of the technology. Patent protection has been applied for, and the compounds used in this research soon will be commercially available.
The researchers received funding from the Life Sciences Institute, the Leukemia & Lymphoma Society and the American Heart Association.
University of Michigan
Oxidative Stress Current Events and Oxidative Stress News RSSScientists find molecular trigger that helps prevent aging and disease
Researchers at Mount Sinai School of Medicine set out to address a question that has been challenging scientists for years: How do dietary restriction-and the reverse, overconsumption-produce protective effects against aging and disease?
'Escaped' proteins add to hearing loss in elderly, UF researchers find
Age-related hearing loss is the most common sensory disorder among the elderly. But scientists are still trying to figure out what cellular processes govern or contribute to the loss.
Pathogen protection and virulence: Dark side of fungal membrane protein revealed
Researchers at the Virginia Bioinformatics Institute (VBI) at Virginia Tech and Montana State University have discovered a fungal protein that plays a key role in causing disease in plants and animals and which also shields the pathogen from oxidative stress.
Reduction in glycotoxins from heat-processing of foods reduces risk of chronic disease
Researchers from Mount Sinai School of Medicine report that cutting back on the consumption of processed and fried foods, which are high in toxins called Advanced Glycation End products (AGEs), can reduce inflammation and actually help restore the body's natural defenses regardless of age or health status.
Phytochemicals in plant-based foods could help battle obesity, disease
The cheeseburger and French fries might look tempting, but eating a serving of broccoli or leafy greens first could help people battle metabolic processes that lead to obesity and heart disease, a new University of Florida study shows.
Study: Added oxygen during stroke reduces brain tissue damage
Scientists have countered findings of previous clinical trials by showing that giving supplemental oxygen to animals during a stroke can reduce damage to brain tissue surrounding the clot.
APP -- Good, bad or both?
New data about amyloid precursor protein, or APP, a protein implicated in development of Alzheimer's disease, suggests it also may have a positive role -- directly affecting learning and memory during brain development.
Nanotech protection
Writing in a forthcoming issue of the International Journal of Nanotechnology, Canadian engineers suggest that research is needed into the risks associated with the growing field of nanotechnology manufacture so that appropriate protective equipment can be developed urgently.
Reactive oxygen in fruit flies acts as a cell signalling mechanism for immune response
For years, health conscious people have been taking antioxidants to reduce the levels of reactive oxygen in their blood and prevent the DNA damage done by free radicals, which are the result of oxidative stress. But could excessive use of antioxidants deplete our immune systems?
Lead in bone associated with increased risk of death from cardiovascular disease in men
Growing evidence shows that exposure to lead in the environment is associated with cardiovascular disease, including increased risk of hypertension.
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