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Enlisting a Natural Enzyme in the Fight Against Cancer

by Gregg Casillo

Radiation and chemotherapy can be effective tools to combat the growth of cancerous cells, but unfortunately the side effects from these treatments make some people sick. Recent research conducted by a UK toxicologist, however, suggests that by incorporating a natural body enzyme into existing treatments, the result might be much less toxic for patients.

Photo of Daret St. ClairDaret St. Clair, a professor in the UK Chandler Medical Center, is studying the antioxidant enzyme manganese superoxide dismutase (MnSOD) that may suppress the growth and even eventually help eradicate the existence of cancer in humans.

"We're still far away from a non-toxic drug that can stop cancer, but the good news is that this enzyme we've been working with is a natural body enzyme," St. Clair says. "It is non-toxic, which makes it much better than any drug or chemical prevention ever known."

In 1998 St. Clair received a three-year grant for approximately $600,000 from the National Cancer Institute to study the effectiveness of this enzyme in suppressing cancerous tumors. Her previous research has shown that this enzyme, which is located in the mitochondria (the energy producers) of the cell, slows the growth of cancer. Antioxidants like MnSOD are believed to offer protection against free-radicals, molecules with unpaired electrons that move through the human body and destroy proteins, carbohydrates, lipids, and nucleic acids.

Primarily because of its antioxidant value, MnSOD has been studied since its discovery in 1979, but St. Clair's research is distinctive in that she is researching the enzyme's potential to regulate cancer cells. "Our lab is one of the two leading groups in the country with this particular focus on cancer research," says St. Clair, whose investigative team consists of nearly a dozen junior faculty, postdocs, graduate students and research associates.

She discovered the value of MnSOD while researching its protective role against an anticancer drug called adriamycin (ADR). Adriamycin causes severe cardiac toxicity in lab animals, especially in the mitochondria of their cells. During the study, St. Clair inserted genes that code for MnSOD into cancer cells found in mice. Unexpectedly, the metastasis of the tumors was blocked.

"We then had critical evidence that showed mitochondria might be important in regulating cancer," St. Clair says. With Kelly Kiningham, a research assistant professor, St. Clair began examining the ability of MnSOD to regulate cancer proteins. While studying an aggressive form of cancer called fibrosarcoma in mice, Kiningham inserted a gene that encodes the MnSOD enzyme. The enzyme regulated the activity of protein produced by a family of genes called the jun and BCL genes, which St. Clair says her team thinks is responsible for cancerous fibrosarcoma growth and death respectively.

Based on these studies, St. Clair, Kiningham, research associate Judy Hines, and postdoctoral fellow Yunfeng Zhao are studying the mechanisms by which MnSOD suppresses cancer development and at what point in the genetic process cancer can be stopped from spreading. "What we're trying to find out is at what point the normal cell first becomes cancerous, and what role MnSOD might play at this stage," says St. Clair.

While St. Clair is "cautiously optimistic" about the direction of this research, she says that much more research will need to be done in the years ahead.