Navigation Links
Small molecules inhibit growth of human tumor cells

Researchers from the Cancer Institute at NYU Langone Medical Center have identified three novel small molecules that interrupt a crucial cellular communication pathway that regulates many aspects of development and cancer. The finding, published in the April 12, 2011 issue of the Proceedings of the National Academy of Sciences and featured on its cover, could provide the basis for innovative therapies for colorectal cancer and other diseases associated with aberrations in this pathway.

"Our study demonstrates that the three newly identified compounds are capable of blocking cell proliferation in cancerous human tumor biopsy cells," said Ramanuj DasGupta, PhD, assistant professor of Pharmacology at NYU School of Medicine and the NYU Cancer Institute, and the scientific director of the NYU RNAi Core Screening Facility.

Dr. DasGupta and his colleagues identified the molecules as inhibitors of the Wnt signaling pathway. This pathway is of special interest to scientists because it controls many biological processes by promoting cell-to-cell communication. Many previous studies have shown that cancers in the liver, breast, skin, and especially the colon, are associated with abnormal signaling activity in this pathway. However, it has been difficult to find potential therapeutic agents aimed at the Wnt pathway.

"These molecules hold a lot of promise towards future Wnt-based drug development for cancer treatments," says Dr. DasGupta. "They may allow the compounds to be used for specific therapeutic purposes in humans to induce the death of Wnt-dependent or Wnt addicted cancer cells and tumor tissues without affecting the growth and proliferation of normal healthy cells."

The scientists demonstrated that the molecules suppressed the activity of the Wnt signaling pathwaywithout disrupting other cellular functionsin human colon cancers from biopsies, in colon cancer cell lines, and in a mouse tumor-xenograft model. In all instances, the inhibitors stopped the proliferation of cancerous cells in the laboratory dish or in the mouse.

"To date, no therapies for the control of Wnt-driven tumors have been available for colon cancer, lung cancer, leukemia, and other forms of the disease caused by mutations in the Wnt pathway," said Robert A. Nagourney, MD, of Rational Therapeutics in Long Beach, California, who is one of the study's authors. "The findings in our human tissue model give us real hope that these compounds will have important implications in future clinical therapy and the development of an effective Wnt inhibitor."

The Wnt pathway is complex and only partially understood. Wnt genes bind to receptors on the surface of cells, provoking a reaction (or a "signaling cascade") within the cell that ultimately allows various "downstream effector proteins" to go into action. One of these proteins, called β catenin, moves into the nucleus and oversees the activation of genes often associated with cell proliferation and other processes.

In the study, the researchers used an innovative, integrated screening platform combining RNA interference (RNAi) -technology and high-throughput chemical genetic screening to examine the potency of 14,977 compounds on the activity of the Wnt pathway. This targeted screening methodology helped identify the three promising novel inhibitors capable of blocking Wnt target genes in various mammalian cancer cell lines including human colon and breast cancer cells. Foster C. Gonsalves, PhD, first author of the study and post-doctoral fellow in Dr. DasGupta's lab, helped develop this technique.

"While more exploratory research of these promising compounds is needed, these small molecules identified in the RNAi screens can serve as prototypes for the development of future antitumor drugs targeting the Wnt signaling pathway in different Wnt-associated cancers," says Dr. DasGupta. "Similar RNAi-based integrated screening technology should be widely applicable to a variety of other signaling pathways implicated in human disease."

This study highlights the strength of high-throughput RNAi-based genome-wide or genome-scale modifier screens currently being performed at NYU's RNAi Screening Facility, according to Dr. DasGupta. The state-of-the-art functional genomic approach continues to help answer basic biological questions in cellular signaling and better define the Wnt pathway, he says.


Contact: Lauren Woods
NYU Langone Medical Center / New York University School of Medicine

Related medicine news :

1. Genes Play Role in Prognosis With Non-Small Cell Lung Cancers
2. Certain genetic profiles associated with recurrence-free survival for non-small cell lung cancer
3. Small Increase in Diabetes Risk Noted in Statin Patients
4. Small to Mid-Sized Hospitals Turn to Orion Health to Implement Health IT Solutions for Improved Patient Care and Outcomes
5. Media, small businesses invited to ACS Webinar on ways to take advantage of Chinas dynamic growth
6. Small Time Company Rolls into the Big League: Trigger Point Performance Therapy Selected to Attend Athletes' Performance NFL Combine Preparation Program
7. Visual Cues that Improve Walking for People with Movement Disorders - Study Shows Small Change in Arrangement Can Make a Big Difference in Improvement Gained
8. Small Dogs Traced Back to Middle Eastern Wolf
9. Landrieu Comments on Presidents Small Business Health Care Report
10. Small molecule with high impact
11. A Small Grass-roots Non-profit, Announces That They Haven't Gone Away and are Still Alive with Helping the Disadvantaged Children in Ukraine
Post Your Comments:
Related Image:
Small molecules inhibit growth of human tumor cells
(Date:11/27/2015)... ... November 27, 2015 , ... MPWH, the No.1 Herpes-only dating community in the world, ... Table 1-1 ). More than 3.7 billion people under the age of 50 – ... according to WHO's first global estimates of HSV-1 infection . , "The data shocks ...
(Date:11/27/2015)... ... November 27, 2015 , ... Intellitec Solutions ... SL User Group (MSDSLUG). Recognized as Microsoft’s official group for end users of ... SL software users, partners, industry experts and representatives. Intellitec Solutions’ membership status demonstrates ...
(Date:11/27/2015)... MINNEAPOLIS, Minn. (PRWEB) , ... November 27, 2015 ... ... you start failing. Secura Consultants has prided itself for not only fulfilling the ... best income protection solutions at an affordable price and providing top-tier customer service. ...
(Date:11/27/2015)... (PRWEB) , ... November 27, 2015 , ... CBD ... Accreditation of Allied Health Education Programs (CAAHEP) awarded accreditation to its Diagnostic Medical Sonography ... CAAHEP accredited colleges, as only one of twelve colleges and universities in the state ...
(Date:11/27/2015)... Rosa, CA (PRWEB) , ... November 27, 2015 , ... ... Northern California Medical Associates, Inc. and Dr. Tucker Bierbaum with Emergency Medicine at ... meeting. They observed that both STEMI and Sepsis conditions present in similar ways and ...
Breaking Medicine News(10 mins):
(Date:11/27/2015)... PHILADELPHIA , Nov. 27, 2015  Lannett ... that it has completed the acquisition of Kremers ... pharmaceuticals subsidiary of global biopharmaceuticals company UCB S.A. ... --> Lannett has acquired KU from UCB ... to certain adjustments, including a customary working capital ...
(Date:11/26/2015)... Un nuevo enfoque combina la ... cáncer avanzado.   --> Un nuevo ... Bremachlorin para el cáncer avanzado.   --> ... la terapia fotodinámica de Bremachlorin para el cáncer avanzado. ... --> Clinical Cancer Research . --> ...
(Date:11/26/2015)... --> --> Juntendo University Hospital ... weighting of MRI for patients with Multiple Sclerosis (MS) ... with SyntheticMR in order to use SyMRI in clinical research ... generate multiple contrast images from a single scan and adjust ... it possible to both fine tune images and recreate additional ...
Breaking Medicine Technology: