August 23, 2004
Bright idea could doom cancer and viruses, say Purdue scientists
WEST LAFAYETTE, Ind. Cancer and viruses may someday find themselves blinded by the light of therapies based on recent Purdue University chemistry research.
A team of scientists including Harry Morrison has developed a group of rhodium-based compounds that, when exposed to light, can kill tumor cells and deactivate a virus closely related to the West Nile and yellow fever viruses. Unlike the ordinary substances used for chemotherapy, these chemicals are not harmful to the body in general they only become lethal to DNA when activated by light of a specific frequency. While therapies based on the discovery are likely many years away, the compounds could have potential as anticancer agents and for blood sterilization.
"We have proven in principle that light and chemistry together can destroy tumor cells and the Sindbis virus, a member of a group of viruses that cause encephalitis, fever and arthritis," said Morrison, who is professor of chemistry and former dean of Purdue's School of Science. "This research offers hope that someday we may be able to replace standard chemotherapy drugs with others that are far less generally harmful to a patient's body and guarantee safe, sterile blood for transfusions."
The research, which appears in the current (Aug. 23) issue of Inorganic Chemistry, was conducted by lead author Elton L. Menon along with Rushika Perera, Richard J. Kuhn and Morrison, all of Purdue, and Maribel Navarro of the Instituto Venezolano de Investigaciones Cientificas, Venezuela.
Chemotherapy has long made use of platinum-based compounds to poison cancer cells. These compounds bind DNA in the cellular nucleus and render the cell unable to reproduce, effectively destroying it. The trouble is, such chemicals also kill many other healthy cells in the body in the process.
"That's the reason cancer patients often lose their hair," Morrison said. "Hair cells, like many others in the patient's body, are also destroyed by these platinum-based chemotherapy drugs. So for a long time, physicians have sought other substances they have more control over. If we had a drug we could activate when it reached a certain place in the body and nowhere else it would reduce the stress on the rest of a cancer patient's system."
Morrison's group experimented with several different chemical complexes that use rhodium, a rare metal, instead of platinum. Eventually they found one compound that was able to damage DNA in living cells in a manner similar to platinum chemotherapy drugs, but with one exception it remains benign until irradiated with a light beam.
"Anticancer therapies could, in theory, be developed using such photo-activated rhodium complexes," Morrison said. "The interior of the body is dark, but it might be possible to thread a fiberoptic cable through the arteries and flood a tumor with light. Some lasers are also capable of shining through tissue without damaging it, and they might also be candidates for light delivery."
The compound known as DPPZPHEN, an abbreviation of its long chemical name also has potential as an antiviral or blood sterilizing agent because it is lethal to any nucleic acid it encounters, including the RNA found in viruses.
"Our study also found the rhodium complex capable of rendering the Sindbis virus inert," Morrison said. "Since blood cells and platelets do not themselves have nucleic acid, they are safe from the compound. But it is potentially possible to purify blood of foreign organisms and viral particles with the rhodium complex and light exposure before it is used in transfusions. It could make for a safer blood supply."
Each of these applications, however, is likely years from development, Morrison said.
"We have only proven in principle that such therapies are possible," he said. "But our experiments have only been on tumor cells in the laboratory, not in living animals. It will require further research to determine how rhodium-based drugs could be created."
Some of that research will need to cover issues that Morrison's group has considered, though not addressed, such as the specific frequencies of light to be used and the compound's level of toxicity.
"Another issue is how to keep these compounds from getting scavenged up by the blood before they reach their targets, which tends to happen because of their adhesion to blood proteins," Morrison said. "But I believe the results are promising for the future of the fight against cancer and viruses, and I hope other groups will continue the work we have begun."
This research was funded in part by the National Institutes of Health.
Morrison and Kuhn are associated with the Purdue Cancer Center. One of just eight National Cancer Institute-designated basic research facilities in the United States, the center attempts to help cancer patients by identifying new molecular targets and designing future agents and drugs for effectively detecting and treating cancer.
Writer: Chad Boutin, (765) 494-2081, firstname.lastname@example.org
Source: Harry Morrison, (765) 494-5246, email@example.com
Purdue News Service: (765) 494-2096; firstname.lastname@example.org
Phototoxicity Against Tumor Cells
An octahedral rhodium complex (cis-dichloro(dipyrido[3,2a2'3'c]phenazine)(1,10-phenantroline) rhodium(III) chloride; DPPZPHEN) has been prepared that can penetrate tumor cell membranes and the Sindbis viral capsid. The compound is phototoxic to these entities when irradiated with UVA light. Model studies with calf thymus and supercoiled plasmid DNA indicate that the complex can both bind with, and nick, nucleic acid. Analysis of Sindbis virus, following irradiation with the metal complex, confirmed that the viral genome was rendered non-infectious by this treatment.
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