Three novel small molecules that interrupt a crucial cellular communication pathway that regulates many aspects of development and cancer have been identified by an Indian-origin scientist and his colleagues.
These could provide the basis for innovative therapies for colorectal cancer and other diseases associated with aberrations in this pathway.
Ramanuj DasGupta, assistant professor of Pharmacology at New York University School of Medicine 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.
"Our study demonstrates that the three newly identified compounds are capable of blocking cell proliferation in cancerous human tumor biopsy cells," said DasGupta.
"These molecules hold a lot of promise towards future Wnt-based drug development for cancer treatments," he said.
"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 pathway-without disrupting other cellular functions-in 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.
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.
The study is published in the current issue of Proceedings of the National Academy of Sciences.