Wnt Signaling Pathway Inhibitors Block Growth of Human Colon Cancer Cells

An innovative, integrated screening platform combining RNA interference (RNAi)-technology and high-throughput chemical genetic screening was used to identify inhibitors of the Wnt signaling pathway, which is active in many types of cancer.

Investigators at New York University (New York, USA) combined RNAi-technology and high-throughput chemical genetic screening to examine the potency of 14,977 compounds on their ability to inhibit activity of the Wnt pathway.

They reported in the April 12, 2011, issue of the journal Proceedings of the [US] National Academy of Sciences that three of the compounds examined were capable of blocking Wnt target genes in various mammalian cancer cell lines including human colon and breast cancer cells. Furthermore, these Wnt inhibitors were specifically cytotoxic to human colon tumor-biopsy cultures as well as colon cancer-cell lines that exhibited deregulated Wnt signaling.

"Our study demonstrates that the three newly identified compounds are capable of blocking cell proliferation in cancerous human tumor biopsy cells,” said senior author Dr. Ramanuj DasGupta, assistant professor of pharmacology at New York University. "These molecules hold a lot of promise towards future Wnt-based drug development for cancer treatments. 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.”

"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.”

Related Links:
New York University