[ Back to EurekAlert! ] Public release date: 20-Apr-2009
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Contact: Karen Mallet
km463@georgetown.edu
215-514-9751
Georgetown University Medical Center

Chemopreventive isothiocyanates selectively depletes mutant p53 in tumor cells

Denver, Colo. Researchers at Lombardi Comprehensive Cancer Center at Georgetown University Medical Center have demonstrated that naturally-occurring compounds can selectively deplete mutant p53 and restore "wild type" function to p53 in a variety of tumor cells.

Mutations in the p53 tumor suppressor gene which is involved in apoptosis and DNA repair occur in about half of all human tumors. p53 often acts as a checkpoint preventing abnormal cells from continuing to grow and divide. However mutations in p53 gene are one way that pre-cancerous cells overcome normal cellular controls and replicate without restraint.

This study demonstrates for the first time that phenethyl isothiocyante (PEITC), a naturally-occurring compound, can selectively deplete mutant p53. The authors also made an intriguing observation that the depletion of mutant p53 in human cancer cells is accompanied by restoration of the wild type p53. PEITC is a member of the isothiocyanate family compounds found in cruciferous vegetables, such as watercress, broccoli and cabbage. PEITC has been shown to have cancer preventive activity.

The researchers found that PEITC not only decreases the level of mutated p53 protein in tumor cells, but also restores the "wild type" or normal activity to mutated p53. The effect of this is that tumor cell lines with mutant p53 became more sensitive to PEITC-induced cytotoxicity than tumor cells with wild type p53, suggesting that the normal p53 checkpoint control pathways have been restored in the mutant p53-expressing tumor cells. This novel finding suggests that the PEITC and other compounds in the isothiocyante family could play important role in both cancer prevention and treatment of human cancers with mutant p53.

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About Lombardi Comprehensive Cancer Center

The Lombardi Comprehensive Cancer Center, part of Georgetown University Medical Center and Georgetown University Hospital, seeks to improve the diagnosis, treatment, and prevention of cancer through innovative basic and clinical research, patient care, community education and outreach, and the training of cancer specialists of the future. Lombardi is one of only 41 comprehensive cancer centers in the nation, as designated by the National Cancer Institute, and the only one in the Washington, DC, area. For more information, go to http://lombardi.georgetown.edu.

About Georgetown University Medical Center

Georgetown University Medical Center is an internationally recognized academic medical center with a three-part mission of research, teaching and patient care (through Georgetown's affiliation with MedStar Health). GUMC's mission is carried out with a strong emphasis on public service and a dedication to the Catholic, Jesuit principle of cura personalis -- or "care of the whole person." The Medical Center includes the School of Medicine and the School of Nursing and Health Studies, both nationally ranked, the world-renowned Lombardi Comprehensive Cancer Center and the Biomedical Graduate Research Organization (BGRO), home to 60 percent of the university's sponsored research funding.



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