Science Current Events | Science News | Brightsurf.com
 
Email a Friend Send to a friend
Printer Friendly Print UNC study: Tinkering with the circadian clock can suppress cancer growth

UNC study: Tinkering with the circadian clock can suppress cancer growth

February 04, 2009

CHAPEL HILL - Researchers at the University of North Carolina at Chapel Hill have shown that disruption of the circadian clock - the internal time-keeping mechanism that keeps the body running on a 24-hour cycle - can slow the progression of cancer.

The study disputes some of the most recent research in the field indicating that alteration of this daily cycle predisposes humans and mice to cancer. The UNC researchers found that genetically altering one of four essential "clock" genes actually suppressed cancer growth in a mouse model commonly used to investigate cancer. The findings could enable clinicians to reset the internal clock of each cancer cell to render it more vulnerable to attack with chemotherapeutic drugs.




"Adjusting the clock in this way could certainly be a new target for cancer treatment," said senior study author Aziz Sancar, M.D., Ph.D., a member of the UNC Lineberger Comprehensive Cancer Center and Sarah Graham Kenan Professor of Biochemistry and Biophysics in the UNC School of Medicine. Sancar is also a member of the National Academy of Sciences, the Turkish Academy of Sciences and the American Academy of Arts and Sciences.

"Our study indicates that interfering with the function of these clock genes in cancer tissue may be an effective way to kill cancer cells and could be a way to improve upon traditional chemotherapy," Sancar said. His findings appear February 2, 2009 in the online early edition of the Proceedings of the National Academy of Sciences.

Previous research has shown that the disruption of the body's natural circadian rhythms affects people's health. One of the largest epidemiological studies ever performed, the Nurses' Health Study, found that nurses who worked the night shift had a higher incidence of breast cancer than those who worked days. Another study of flight attendants whose internal biological clocks had been wrecked by travel on transatlantic flights produced similar findings.

Yet when scientists, including Sancar, began to tinker with the molecular mechanisms within the internal clocks of animal models, they did not always see such an effect. Circadian rhythms in humans and in mice are controlled by "clock genes," four of which are absolutely essential. In a study four years ago, Sancar found that deleting the clock gene cryptochrome in mice did not increase the incidence of cancer as had previously been expected.

While altering the clock gene did not cause cancer in otherwise normal mice, Sancar and his colleagues wanted to see if it would accelerate the development of tumors in a mouse model that is already predisposed to cancer. Therefore, in this study they modified the cryptochrome gene in mice that also had defects in a gene called P53, which is mutated in nearly half of human cancers. The researchers found that disturbing the internal clock in these mice did not speed up the onset of cancer, but instead had the opposite effect - it extended their lives by 50 percent.

The researchers then wanted to know how interfering with the cryptochrome gene had reduced the incidence of cancer. By closely examining the series of biological events in the disease's development, they determined that the mutation of this clock gene reactivates the intracellular signals that can eliminate cancerous cells. Sancar said this tactic essentially makes cancer cells more likely to commit cell suicide - through a process known as apoptosis - in response to the stresses of UV radiation or chemotherapy.

"These results suggest that altering the function of this clock gene, at least in the 50 percent of human cancers associated with p53 mutations, may slow the progression of cancer," Sancar said. "In combination with other approaches to cancer treatment, this method may one day be used to increase the success rate of remission."

The research was supported by the National Institutes of Health. Study co-authors from Sancar's UNC laboratory include the lead author and postdoctoral fellow Nuri Ozturk, Ph.D.; Jin Hyup Lee, a graduate student; and postdoctoral fellow Shobhan Gaddemeedhi, Ph.D.


The study follows the recent publication earlier this month of another paper from Sancar's laboratory in the Proceedings of the National Academy of Sciences. It suggested that chemotherapy treatment for cancer is most effective at certain times of day because that is when a particular enzyme system - one that can reverse the actions of chemotherapeutic drugs - is at its lowest levels in the body.

University of North Carolina School of Medicine



Related Circadian Clock Current Events and Circadian Clock News Articles Circadian Clock Current Events and Circadian Clock News RSS Circadian Clock Current Events and Circadian Clock News RSS
New paper describes connections between Circadian and metabolic systems
A paper by University of Notre Dame biologist Giles Duffield and a team of researchers offers new insights into a gene that plays a key role in modulating the body's Circadian system and may also simultaneously modulate its metabolic system.

Faulty body clock may make kids bipolar
Malfunctioning circadian clock genes may be responsible for bipolar disorder in children. Researchers writing in the open access journal BMC Psychiatry found four versions of the regulatory gene RORB that were associated with pediatric bipolar disorder.

Circadian surprise: A heat sensor for body-clock synchronization
New research on the fruit-fly brain points to a possible mechanism by which temperature influences the body clock, according to scientists from Queen Mary, University of London.

U-M discovery about biological clocks overturns long-held theory
University of Michigan mathematicians and their British colleagues say they have identified the signal that the brain sends to the rest of the body to control biological rhythms, a finding that overturns a long-held theory about our internal clock.

Plants' internal clock can improve climate-change models
The ability of plants to tell the time, a mechanism common to all living beings, enables them to survive, grow and reproduce.

MicroRNAs grease the cell's circadian clockwork
Most of our cells possess an internal clock, a group of genes displaying a cyclic expression pattern that reaches a peak once a day.

A Biological Basis for the 8-Hour Workday?
The circadian clock coordinates physiological and behavioral processes on a 24-hour rhythm, allowing animals to anticipate changes in their environment and prepare accordingly. Scientists already know that some genes are controlled by the clock and are turned on only one time during each 24-hour cycle.

Scripps research scientists model 3D structures of proteins that control human clock
In an Early Edition issue of The Proceedings of the National Academy of Sciences (PNAS) on April 9, 2009, the researchers report that they have been able to determine the molecular structure of a plant photolyase protein that is surprisingly similar to two cryptochrome proteins that control the "master clock" in humans and other mammals.

Missing or mutated 'clock' gene linked to vascular disease
The circadian clocks that set the rhythmic motion of our bodies for wakeful days and sleepy nights can also set us up for vascular disease when broken, Medical College of Georgia researchers say.

UNC study supports role of circadian clock in response to chemotherapy
For years, research has hinted that the time of day that cancer patients receive chemotherapy can impact their chances of survival. But the lack of a clear scientific explanation for this finding has kept clinicians from considering timing as a factor in treatment.
More Circadian Clock Current Events and Circadian Clock News Articles
Circadian Clock

Circadian Clock
Scarring Fields (Primary Contributor)



Handbook of Behavioral Neurobiology, Volume 12: Circadian Clocks (Handbooks of Behavioral Neurobiology)

Handbook of Behavioral Neurobiology, Volume 12: Circadian Clocks (Handbooks of Behavioral Neurobiology)
by Joseph S. Takahashi (Editor), Fred W. Turek (Editor), Robert Y. Moore (Editor)

The Handbook of Behavioral Neurobiology series deals with the aspects of neurosciences that have the most direct and immediate bearing on behavior. It presents the most current research available in the specific areas of sensory modalities. This volume explores circadian rhythms.

  Circadian Clocks
by The Jarts



BioBrite Sunrise Radio Advanced Model - Platinum with 2 FREE replacement bulbs

BioBrite Sunrise Radio Advanced Model - Platinum with 2 FREE replacement bulbs
by BioBrite

BioBrite's newest product, the SunRise Clock Radio is derived from medical research on light and human behavior. In the early morning, the human biological clock is sensitive to low intensity light. So, waking to a slowly increasing light can result in a smoother, more natural transition to wakefulness. While gently waking with a simulated sunrise, now you can let the 6:52 weather report on the FM radio inform you of a sunny day before you even open your eyes. If you'd like to fall asleep with music playing in the background, you can program the radio to fade out after a period of time which you can adjust. Other features include the choice of fade up and fade down over 15, 30, 45, or 60 minutes; snooze feature; the security feature of random evening lighting; fade to nightlight; a back...

Clockwork Genes: Discoveries in Biological Time

Clockwork Genes: Discoveries in Biological Time
Also With: Micahel Rosbash (Primary Contributor), Joseph S. Takahshi (Primary Contributor)

The Sun Rises and sets, tides ebb and flow, and the seasons change. Circadian clocks -- internal timekeepers that govern fluctuations in behavior and physiology on a 24-hour cycle -- have helped organisms adapt to the rhythms of life on Earth.

In recent years, scientists have gained a greater understanding of circadian clocks. These four lectures highlight the research of two biomedical scientists who have made groundbreaking discoveries elucidating the molecular basis of circadian clocks.

In these lectures -- enhanced by scientific animations and student questions -- the scientists explain what circadian clocks are, how they work, and what relevance this knowledge might have for human health. They also describe the scientific methods that led to their...

Circadian Clocks

Circadian Clocks
The Jarts (Primary Contributor)



  Circadian Clocks: Proceedings of the Feldafing Summer School 7-18 September 1964
by Jurgen (editor) Aschoff (Author)



Internal Clock

Internal Clock
Circadian Rhythms (Primary Contributor)



  The Psysiological Clock: Circadian Rythms and Biological Chronometry the heidelberg science library Vol 1
by Professor Erwin Bunning (Author)



The Daily Ground

The Daily Ground
Circadian Rhythms (Primary Contributor)



© 2009 BrightSurf.com