University of Iowa News
June 1, 2006
UI Cancer Researchers Receive Grant To Study Cell Cycle Checkpoints
University of Iowa Roy J. and Lucille A. Carver College of Medicine researchers in the UI Holden Comprehensive Cancer Center have been awarded a five-year, $1.5 million grant from the National Cancer Institute to investigate a new hypothesis about how the mammalian cell cycle is regulated.
The cell cycle is the normal, orderly growth and division of cells. This process, also known as proliferation, is usually tightly controlled, but in cancers the process goes awry and malignant cells proliferate in an uncontrolled manner. Understanding the genetic and biochemical mechanisms that govern the cell cycle could lead to new and better cancer therapies that kill cancer cells but are not toxic to normal cells.
The research team, led by Prabhat Goswami, Ph.D., UI assistant professor of radiation oncology in the Free Radical and Radiation Biology Graduate Program, will test the idea that reactive oxygen species (ROS) produced by cells control the progression from the G1 phase of the cell cycle to the S phase, in which DNA is synthesized.
For many years, ROS such as hydrogen peroxide and superoxide were thought to be toxic by-products of living in an oxygen atmosphere. However, recent studies suggest that low levels of ROS could act as important signaling molecules regulating many cellular processes including proliferation.
ROS molecules are important players in the so-called redox state of the cell. The redox state is the balance between oxidation and reduction reactions in cells that are responsible for producing energy and maintaining cellular functions.
Goswami and his colleagues have discovered that the cellular redox state varies during the cell cycle, and a pro-oxidant signal is apparently necessary for cells to progress into S-phase of the cell cycle, in which DNA is synthesized, and the M-phase, in which cells divide.
In non-cancer cells, changing the cellular redox state with an antioxidant prevents progress into the S-phase of the cycle. The same treatment does not affect the cancer cell cycle. These results suggest that the redox environment regulates cell cycle progression, and that redox control of the cell cycle could be different in normal cell and in cancer cells.
"Normal cells with redox-sensitive checkpoints would halt cell cycle progression in response to agents that disturb the cellular redox state. In contrast, cancer cells with defects in redox-sensitive checkpoints will continue to proliferate," explained Goswami, who also is a co-director of the Free Radical Research Core in the Holden Comprehensive Cancer Center at the UI. "If redox control of the cell cycle is different in normal cells than in cancer cells, that difference potentially could be exploited to develop new redox-based cancer therapies."
A clearer picture of the role that intracellular redox states play in cell cycle progression should lead to a better understanding of normal and aberrant cellular proliferation.
"Since proliferative disorders are central to a variety of human disease conditions, we believe our efforts will stimulate a novel area of research," Goswami added.
University of Iowa Health Care describes the partnership between the UI Roy J. and Lucille A. Carver College of Medicine and UI Hospitals and Clinics and the patient care, medical education and research programs and services they provide. Visit UI Health Care online at www.uihealthcare.com.
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