{"id":3891,"date":"2009-02-05T17:40:00","date_gmt":"2009-02-05T22:40:00","guid":{"rendered":"https:\/\/www.med.unc.edu\/biochem\/tinkering-with-the-circadian-clock-can-suppress-cancer-growth\/"},"modified":"2018-08-01T10:17:40","modified_gmt":"2018-08-01T14:17:40","slug":"tinkering-with-the-circadian-clock-can-suppress-cancer-growth","status":"publish","type":"post","link":"https:\/\/www.med.unc.edu\/biochem\/news\/tinkering-with-the-circadian-clock-can-suppress-cancer-growth\/","title":{"rendered":"Tinkering with the circadian clock can suppress cancer growth"},"content":{"rendered":"
\n

Researchers in Aziz Sancar\u2019s group in the Department of Biochemistry & Biophysics at UNC-Chapel Hill have shown that disruption of the circadian clock \u2013 the internal time-keeping mechanism that keeps the body running on a 24-hour cycle \u2013 can slow the progression of cancer.<\/p>\n

\n
\n \"image2\"\/
Aziz Sancar and postdoc, Nuri Ozturk
\n <\/figcaption><\/figure>\n<\/div>\n
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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 \u201cclock\u201d 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.<\/p>\n

\u201cAdjusting the clock in this way could certainly be a new target for cancer treatment,\u201d 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.<\/p>\n

\u201cOur 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,\u201d Sancar said. His findings appear in the Feb. 2, 2009 online early edition of the Proceedings of the National Academy of Sciences.<\/p>\n

Previous research has shown that the disruption of the body\u2019s natural circadian rhythms affects people\u2019s health. One of the largest epidemiological studies ever performed, the Nurses\u2019 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.<\/p>\n

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 \u201cclock genes,\u201d 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.<\/p>\n

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 \u2013 it extended their lives by 50 percent.<\/p>\n

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\u2019s 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 \u2013 through a process known as apoptosis \u2013 in response to the stresses of UV radiation or chemotherapy.<\/p>\n

\u201cThese 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,\u201d Sancar said. \u201cIn combination with other approaches to cancer treatment, this method may one day be used to increase the success rate of remission.\u201d<\/p>\n

The research was supported by the National Institutes of Health. Study co-authors from Sancar\u2019s UNC laboratory include the lead author and postdoctoral fellow Nuri Ozturk, Ph.D.; Jin Hyup Lee, a graduate student; and postdoctoral fellow Shobhan Gaddameedhi, Ph.D.<\/p>\n

The study follows the recent publication earlier this month of another paper from Sancar\u2019s 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 \u2013 one that can reverse the actions of chemotherapeutic drugs \u2013 is at its lowest levels in the body.<\/p>\n

To read the news release about the previous study, go to: Role of circadian clock in response to chemotherapy<\/a><\/p>\n

To read the news release from the NIH, go to: http:\/\/www.nih.gov\/news\/research_matters\/january2009\/01262009chemotherapy.htm<\/a><\/p>\n<\/div>\n<\/div>\n","protected":false},"excerpt":{"rendered":"

<\/p>\n

Researchers in Aziz Sancar’s group in the Department of Biochemistry & Biophysics at UNC-Chapel Hill have shown that disruption of the circadian clock \u2013 the internal time-keeping mechanism that keeps the body running on a 24-hour cycle \u2013 can slow the progression of cancer.<\/p>\n","protected":false},"author":12066,"featured_media":3892,"comment_status":"closed","ping_status":"closed","sticky":false,"template":"","format":"standard","meta":{"_acf_changed":false,"layout":"","cellInformation":"","apiCallInformation":"","footnotes":"","_links_to":"","_links_to_target":""},"categories":[2],"tags":[10,14,4],"class_list":["post-3891","post","type-post","status-publish","format-standard","has-post-thumbnail","hentry","category-news","tag-news_faculty","tag-news_2009","tag-recent-news","odd"],"acf":[],"yoast_head":"\nTinkering with the circadian clock can suppress cancer growth | Biochemistry and Biophysics<\/title>\n<meta name=\"robots\" content=\"index, follow, max-snippet:-1, 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