Enzyme discovery may link underlying processes in cancer and heart disease

September 01, 1999

Scientists at Emory University have discovered a new family of enzymes that appears to play a powerful role in generating the abnormal cell growth that occurs in both cancer and in some forms of cardiovascular disease. The enzymes appear to convert oxygen into a class of molecules known as "reactive oxygen", which has long been implicated in causing damage to cellular molecules such as DNA and in the aging process. The research is reported in the Sept. 2, 1999 issue of Nature.

Through their experiments with Mox1, one of the enzymes in the new class, the Emory scientists, led by biochemist J. David Lambeth, M.D., Ph.D., in collaboration with cardiology researcher Kathy Griendling, Ph.D., found that the reactive oxygen produced by the enzymes functions as a potent growth signal inside cells, instructing cells to divide more rapidly. Abnormal cell division or growth is seen in cancerous cells as well as in some forms of cardiovascular disease.

In the case of cancer, rapid and uncontrolled cell division leads to tumor formation. In cardiovascular disease, abnormal cell growth leads to the formation of plaques seen in hardening of the arteries (atherosclerosis) and in thickening of the blood vessel walls, which causes high blood pressure. Although scientists know that different molecular signals instruct cells to behave in various ways, the cellular mechanisms regulating cell growth have been poorly understood.

Dr. Lambeth and his colleagues first cloned the human Mox1 gene based on its similarity to an enzyme that generates reactive oxygen in neutrophils as a mechanism to kill bacteria. They then introduced the Mox1DNA into mouse cells and were surprised to observe that the cells took on the appearance of cancer cells and divided more rapidly than normal cells. When they injected these transformed cells into mice they found that the cells were extremely powerful in producing tumors.

"Although scientists have known that reactive oxygen is produced by many cancer cells, they have not known whether it is a cause of cancer," Dr. Lambeth says. "These studies show that the reactive oxygen can be a cause rather than a byproduct of cancer and that the Mox1 enzyme or a close relative is the source of the reactive oxygen."

The scientists found that Mox1 also is present in the walls of arterial cells, where it regulates normal cell growth. An overabundance of the enzyme, however, occurs under conditions that lead to hypertension and atherosclerosis, suggesting that Mox1 or other enzymes in its class may be involved in these abnormal processes.

The research also demonstrated that the abnormal cell growth directed by the Mox1 family can be reversed by treatments that remove reactive oxygen from cells. This suggests, says Dr. Lambeth, that novel approaches might be developed to treat cancer, reverse hardening of the arteries or treat high blood pressure, including drugs designed to block this type of enzyme or treatments that destroy reactive oxygen.

Irwin Fridovich, Ph.D., James B. Duke Professor of Biochemistry at Duke University Medical Center, who discovered an enzyme that "detoxifies" reactive oxygen, believes the Emory research will likely lead scientists to try to clarify the specific signaling roles of reactive oxygen and hydrogen peroxide. "One cannot help feeling that we are getting close to knowing how to most usefully intercede in treating and reversing diseases involving abnormal cell proliferation," he notes.

"The discovery of Mox1 by Drs. Lambeth and Griendling and their colleagues could be fundamentally important in developing a new understanding of causes of diseases ranging from cancer and heart disease to stroke and dementia," says Emory cardiologist R. Wayne Alexander, M.D. "These findings could open the door to exciting new approaches to treatment of these common maladies."

The Emory research was funded by the National Institutes of Health.
-end-


Emory University Health Sciences Center

Related Cancer Articles from Brightsurf:

New blood cancer treatment works by selectively interfering with cancer cell signalling
University of Alberta scientists have identified the mechanism of action behind a new type of precision cancer drug for blood cancers that is set for human trials, according to research published in Nature Communications.

UCI researchers uncover cancer cell vulnerabilities; may lead to better cancer therapies
A new University of California, Irvine-led study reveals a protein responsible for genetic changes resulting in a variety of cancers, may also be the key to more effective, targeted cancer therapy.

Breast cancer treatment costs highest among young women with metastic cancer
In a fight for their lives, young women, age 18-44, spend double the amount of older women to survive metastatic breast cancer, according to a large statewide study by the University of North Carolina at Chapel Hill.

Cancer mortality continues steady decline, driven by progress against lung cancer
The cancer death rate declined by 29% from 1991 to 2017, including a 2.2% drop from 2016 to 2017, the largest single-year drop in cancer mortality ever reported.

Stress in cervical cancer patients associated with higher risk of cancer-specific mortality
Psychological stress was associated with a higher risk of cancer-specific mortality in women diagnosed with cervical cancer.

Cancer-sniffing dogs 97% accurate in identifying lung cancer, according to study in JAOA
The next step will be to further fractionate the samples based on chemical and physical properties, presenting them back to the dogs until the specific biomarkers for each cancer are identified.

Moffitt Cancer Center researchers identify one way T cell function may fail in cancer
Moffitt Cancer Center researchers have discovered a mechanism by which one type of immune cell, CD8+ T cells, can become dysfunctional, impeding its ability to seek and kill cancer cells.

More cancer survivors, fewer cancer specialists point to challenge in meeting care needs
An aging population, a growing number of cancer survivors, and a projected shortage of cancer care providers will result in a challenge in delivering the care for cancer survivors in the United States if systemic changes are not made.

New cancer vaccine platform a potential tool for efficacious targeted cancer therapy
Researchers at the University of Helsinki have discovered a solution in the form of a cancer vaccine platform for improving the efficacy of oncolytic viruses used in cancer treatment.

American Cancer Society outlines blueprint for cancer control in the 21st century
The American Cancer Society is outlining its vision for cancer control in the decades ahead in a series of articles that forms the basis of a national cancer control plan.

Read More: Cancer News and Cancer Current Events
Brightsurf.com is a participant in the Amazon Services LLC Associates Program, an affiliate advertising program designed to provide a means for sites to earn advertising fees by advertising and linking to Amazon.com.