Joanna Cosgrove, Online Editor04.12.12
Cancer survival rates are on the rise and so too is research into more effective treatment options. A team of researchers from the National Institutes of Health (NIH) recently completed an early stage look into the role of antioxidants in cancer treatment, identified some that showed potential in multidrug-resistant dividing cancer cells and concluded that antioxidants “are potentially better chemotherapeutic agents than ones currently used.”
Their findings were published online in the Proceedings of the National Academy of Sciences.
In an interview with Nutraceuticals World, Kyungjae Myung, PhD, a senior investigator in the Genetics and Molecular Biology Branch of the National Human Genome Research Institute in Bethesda, MD, said after having studied DNA repair for many years, he believed DNA repair to be a very important mechanism to sustain cellular activity.
“I also believe that DNA repair pathway is a good target for cancer treatment for clinical purpose. It is why I decided to apply understanding of DNA repair to clinical purpose (translational research),” he said. “We developed a new assay that can detect genotoxicity of compounds based on our recent findings of a new biomarker (ATAD5). Our group planned to screen chemical depository to identify better chemotherapeutic agents since many chemotherapeutic agents are genotoxic compounds. To achieve this, we screened small sets of compounds to initiate this large screening and results are the report in the PNAS paper.”
Dr. Myung and his colleagues screened 4000 compounds and identified a total of 22 antioxidants that showed promise; however the standout antioxidants proved to be red-wine derived resveratrol, and plant-origin baicalein, and genistein.
“Treatment of dividing cells with these compounds [resveratrol, genistein, and baicalein] induced DNA damage and resulted in cell death,” the study authors wrote. “Despite their genotoxic effects, resveratrol, genistein, and baicalein did not cause mutagenesis, which is a major side effect of conventional anticancer drugs. Furthermore, resveratrol and genistein killed multidrug-resistant cancer cells. We therefore propose that resveratrol, genistein, and baicalein are attractive candidates for improved chemotherapeutic agents.”
“We do not know exactly whether these three are better than others,” Dr. Myung admitted. “We chose them based on their structure bases that represent different types of antioxidants [and] all experiments in the study were performed with treatment separately.”
In an interview with Bloomberg News, Dr. Myung said that while more studies would be needed before antioxidants could be formally used as resources in cancer treatment, “It’s a much safer chemotherapy agent if it can be developed,” he said.
In fact, the researchers wrote that collectively, their data indicated that although resveratrol, baicalein, and genistein inflicted the same amount of DNA damage and caused a similar level of cell death as widely used chemotherapy agents MMS and cisplatin, “they did not cause serious genomic instabilities either at the chromosomal or nucleotide levels, in contrast to MMS and cisplatin.”
Dr. Myung was quick to caution those who might unwisely consider taking a large-dose antioxidant supplement with the hope of replicating the effect. “The dose that we used for this treatment in a laboratory setting was way higher than you can get from wine or all those antioxidant tablets or you can consume by eating,” he said, adding that antioxidants in high amounts could yield an opposite effect, damaging DNA and killing cells.
Dr. Myung and his colleagues are currently trying to determine if antioxidants could kill specific types of cancer cells. They are also eager to learn if the antioxidants could discriminately kill diseased cells or if they might have an effect on healthy cells as well.
The team is investigating the molecular mechanisms of genotoxicity caused by antioxidants while screening the NIH chemical library to identify more potent chemotherapeutic agents.
Dr. Myung added that the next phase of their research will be to investigate effects of the antioxidants in combination with each other and also in combination with other chemotherapeutic agents. “[The] beneficial effect was less mutagenicity of these antioxidants compared to conventional chemotherapeutic reagents,” he noted.
Their findings were published online in the Proceedings of the National Academy of Sciences.
In an interview with Nutraceuticals World, Kyungjae Myung, PhD, a senior investigator in the Genetics and Molecular Biology Branch of the National Human Genome Research Institute in Bethesda, MD, said after having studied DNA repair for many years, he believed DNA repair to be a very important mechanism to sustain cellular activity.
“I also believe that DNA repair pathway is a good target for cancer treatment for clinical purpose. It is why I decided to apply understanding of DNA repair to clinical purpose (translational research),” he said. “We developed a new assay that can detect genotoxicity of compounds based on our recent findings of a new biomarker (ATAD5). Our group planned to screen chemical depository to identify better chemotherapeutic agents since many chemotherapeutic agents are genotoxic compounds. To achieve this, we screened small sets of compounds to initiate this large screening and results are the report in the PNAS paper.”
Dr. Myung and his colleagues screened 4000 compounds and identified a total of 22 antioxidants that showed promise; however the standout antioxidants proved to be red-wine derived resveratrol, and plant-origin baicalein, and genistein.
“Treatment of dividing cells with these compounds [resveratrol, genistein, and baicalein] induced DNA damage and resulted in cell death,” the study authors wrote. “Despite their genotoxic effects, resveratrol, genistein, and baicalein did not cause mutagenesis, which is a major side effect of conventional anticancer drugs. Furthermore, resveratrol and genistein killed multidrug-resistant cancer cells. We therefore propose that resveratrol, genistein, and baicalein are attractive candidates for improved chemotherapeutic agents.”
“We do not know exactly whether these three are better than others,” Dr. Myung admitted. “We chose them based on their structure bases that represent different types of antioxidants [and] all experiments in the study were performed with treatment separately.”
In an interview with Bloomberg News, Dr. Myung said that while more studies would be needed before antioxidants could be formally used as resources in cancer treatment, “It’s a much safer chemotherapy agent if it can be developed,” he said.
In fact, the researchers wrote that collectively, their data indicated that although resveratrol, baicalein, and genistein inflicted the same amount of DNA damage and caused a similar level of cell death as widely used chemotherapy agents MMS and cisplatin, “they did not cause serious genomic instabilities either at the chromosomal or nucleotide levels, in contrast to MMS and cisplatin.”
Dr. Myung was quick to caution those who might unwisely consider taking a large-dose antioxidant supplement with the hope of replicating the effect. “The dose that we used for this treatment in a laboratory setting was way higher than you can get from wine or all those antioxidant tablets or you can consume by eating,” he said, adding that antioxidants in high amounts could yield an opposite effect, damaging DNA and killing cells.
Dr. Myung and his colleagues are currently trying to determine if antioxidants could kill specific types of cancer cells. They are also eager to learn if the antioxidants could discriminately kill diseased cells or if they might have an effect on healthy cells as well.
The team is investigating the molecular mechanisms of genotoxicity caused by antioxidants while screening the NIH chemical library to identify more potent chemotherapeutic agents.
Dr. Myung added that the next phase of their research will be to investigate effects of the antioxidants in combination with each other and also in combination with other chemotherapeutic agents. “[The] beneficial effect was less mutagenicity of these antioxidants compared to conventional chemotherapeutic reagents,” he noted.
